bluuebunny/crossref_metadata_2025 huggingface dataset:
Depressor and pressor actions of purine nucleosides and nucleotides in the anaesthetized rat
Authors: DELBRO D. , BURNSTOCK G.
Published: December 2008

Depressor and pressor actions of purine nucleosides and nucleotides in the anaesthetized rat.Acta Physiol Scand130, 373–380. Received 12 May 1986, accepted 28 January 1986. ISSN 0001–6772. Departments of Physiology, University of Goteborg, Sweden and Anatomy & Embryology and Centre for Neuroscience, University College, London, UK.

In pentobarbitone‐chloralose anaesthetized rats, the effects of aortic administration of various purine compounds on systemic arterial pressure were investigated. All animals were pretreated with atropine and guanethidine to (largely) eliminate reflex neurogenic cardiovascular adjustments, and drugs influencing purine receptors, prostaglandin synthesis, etc. were used for analytical purposes. The compounds used were adenosine (AD) and its slowly degradable analogue, 2‐chloroadenosine (2‐chloro), adenosine‐5′‐triphosphate (ATP) and its slowly degradable analogues β,γ‐methyleneATP (β,γ‐meATP) and α,β‐methyleneATP (α,β‐meATP). Control cardiac output measurements before, at and after the peak pressure changes in some experiments revealed that they were at least 80% due to changes in systemic resistance, i.e. dominated by shifts in resistance vascular tone. Adenosine, 2‐chloro, ATP and β,γ‐meATP all elicited depressor (vasodilator) responses. 2‐chloro was more potent than AD. Furthermore, the results suggest that the depressor action of ATP involves P1‐purinoceptors, following the rapid degradation of ATP to AD, and probably also other mechanisms. The stable ATP analogues caused prompt pressor (vasoconstrictor) responses, where α,β‐meATP was more potent than β,γ‐meATP. The latter compound also produced delayed (probably P1‐purinoceptormediated) depressor actions, presumably via slow degradation to AD.
Renal degradation and distribution between urinary and venous output of prostaglandins E2and I2
Authors: BUGGE J. F. , VIKSE A. , DAHL E. , KIIL F.
Published: December 2008

Renal degradation and distribution between urinary and venous output of prostaglandins E2and I2Acta Physiol Scand130, 467–474. Received 25 November 1986, accepted 11 February 1987. ISSN 0001–6772. University of Oslo, Institute for Experimental Medical Research, Ullevaal Hospital, Oslo, Norway.

To examine renal degradation and distribution between urine and renal venous blood, prostaglandins E2and I2(PGE2and PGI2), and a metabolite of PGI2, bketo‐PGF1α, were infused into the suprarenal aorta of anaesthetized dogs after blocking prostaglandin synthesis by indomethacin, 10 mg kg‐1body wt iv. During one passage through the kidney 80% of PGE, and only 25% of PGI2and 6‐keto‐PGF1α, were metabolized. Prostaglandin degradation and arterial input were proportional (r> 0.90). To stimulate the intrarenal prostaglandin synthesis in unblocked kidneys, arachidonic acid was infused at rates ranging from 24 to 160 μg min‐1kg‐1body wt. During arachidonic acid and PGE2infusion the urinary excretion of PGE2was about 20% of the renal venous output over a wide range of infusion rates. During arachidonic acid and PGI2infusion urinary excretion of bketo‐PGF1αwas about 10% of total renal output, but failed to increase further when total renal output exceeded 70 pmol min‐1. Further increase in output occurred only in the renal vein. In contrast, during 6‐keto‐PGF1αinfusion the urinary excretion and the renal venous output of this metabolite were related as 1:2 over a wide range of infusion rates. Thus, PGI2is much less degraded by renal tissue than PGE2, and the distribution patterns differ. Similar distributions between urine and renal venous blood during aortic infusion and stimulated intrarenal synthesis suggest a pre‐glomerular vascular origin of both prostaglandins.
Intrathecal noradrenaline has a dose‐dependent inhibitory or facilitatory effect on the flexion reflex in the rat
Authors: WIESENFELD‐HALLIN Z.
Published: December 2008

Intrathecal noradrenaline has a dosedependent inhibitory or facilitatory effect on the flexion in the rat.Acta Physiol Scand130, 507–511. Received 15 January 1987, accepted 27 February 1987. ISSN 0001–6772. Department of Clinical Physiology and Neurophysiology, Huddinge University Hospital, Sweden.

The effect of intrathecal noradrenaline (NA) on the hamstring flexion reflex to subcutaneous electrical shocks was examined in unanaesthetized, decerebrate, spinalized rats. Low doses of NA (200 ng and 2 μg) depressed and high doses (20 μg and 200 μg) facilitated the reflex. It is suggested that the primary effect of NA in the dorsal horn is inhibitory and in the ventral horn excitatory. Furthermore, the neurons mediating these effects are more sensitive to NA in the dorsal horn than in the ventral horn.
Altered shape and size of red blood cells in obese hyperglycaemic mice
Authors: ENGSTRÖM K. G. , TÄLJEDAL I.‐B.
Published: December 2008

Altered shape and size of red blood cells in obese hyperglycaemic mice. Acta Physiol Scand130, 535–543. Received 31 October 1986, accepted 2 March 1987. ISSN 0001–6772. Department of Histology and Cell Biology, University of Umeå, Sweden.

Red blood cells (RBCs) from hyperglycaemic ob/ob‐mice, normoglycaemic controls, and a healthy man were sucked into a narrow capillary, photographed and measured. Mouse RBCs had a smaller diameter than human ones. Although of normal diameter, the ob/ob‐mouse RBCs exhibited increased area and volume, and more frequently than control RBCs had a minimum cylindrical diameter greater that 3 μm. Cross‐sectional profiles with minimum bending resistance were computed for RBCs of mean area and volume. The diameters of these theoretical profiles agreed closely with those empirically observed, in both mice and man. The profile of ob/ob‐mouse RBCs predicted a greater resistance to corpuscle bending than the control profile. It is concluded that changes in shape and size explain the decreased filtrability of diabetic ob/ob‐mouse RBCs. The results also suggest that the actually occuring smooth biconcavity is in general the RBC shape with maximum flexibility.
Effect of L‐Dopa, dopamine, dihydroxyphenyl acetic acid and homovanillic acid on Na, K‐ATPase activity in rat proximal tubule segments
Authors: BERTORELLO A. , APERIA A.
Published: December 2008

Effect of L‐Dopa, dopamine, dihydroxyphenyl acetic acid and homovanillic acid on Na, K‐ATPase activity in rat proximal tubule segments.Acta Physiol Scand130, 571–574. Received 6 November 1986, accepted 16 February 1987. ISSN 0001–6772. Department of Developmental Physiology, St Görans Children's Hospital, Stockholm, Sweden.

We have recently demonstrated that dopamine (DA) inhibits Na, K‐ATPase in single proximal tubule (PCT) segments dissected from previously collagenase perfused rat kidney. The aim of the present study was to ascertain whether this effect was directly mediated by DA or if DA was the precursor of an inhibitor. When PCT segments were incubated with I.‐Dopa, Na,K‐ATPase was significantly lower than in vehicle incubated tubules. Inhibition of dopa decarboxylase abolished the effect of L‐Dopaon Na,K‐ATPase activity. The metabolites of DA, 3, 4‐dihydroxyphenyl acetic acid (DPAC) and homovanillic acid (HVA) both inhibited Na,K‐ATPase activity in doses higher than 10‐‐6M. Both HVA and DPAC 10‐‐4M caused approximately 35% inhibition. Dopamine inhibited Na,K‐ATPase activity even in a dose as low as 10‐‐7M. Maximal inhibition (>60%) was found with DA‐5M. Na,K‐ATPase activity was significantly lower in tubules exposed to DA 10‐‐4and 10‐‐5M than in tubules exposed to DPAC or HVA 10‐‐4and 10‐‐5m. Dopamine produced in proximal tubule cells from L‐Dopa, is an active inhibitor of the Na,K‐pump in these cells. The DA metabolites DPAC and HVA are less potent Na,K‐pump‐inhibitors.
Comparison of atriopeptins II and III, VIP andβ2‐‐adrenoceptor‐evoked relaxations of the two layers of smooth muscle in the rat portal vein
Authors: BRÅTVEIT M. , RYDNINGEN H. T. , HELLE K. B.
Published: December 2008

Comparison of atriopeptins II and III, VIP andβ2‐‐adrenoceptor‐evoked relaxations in the two layers of smooth muscle in the rat portal vein.Acta Physiol Stand130, 593–599. Received II November 1986, Accepted 26 February 1987. ISSN 0001–6772. Department of Physiology, University of Bergen, Norway.

The relative importance of vascular relaxations induced by atriopeptins (AP), theβ‐adrenoceptor agonist isoprenaline and of the neuropeptide VIP was studiedin uitroon circular and longitudinal preparations of the rat portal vein. Two members of the rat atriopeptins (AP II and III) were equipotent with respect to relaxation of the spontaneously contracting outer, longitudinal layer and of theα1‐‐contracted inner, circular layer. The potency for AP II was about 13 times lower in the inner (pD2= 7.48±0.73,n= 6) than in the outer layer (pD2= 8.60 ±0.34,n =6). No significant difference was apparent between the intrinsic activities for AP II in the two layers. The potencies for AP II were for both layers higher than those for VIP while the intrinsic activities for AP II were significantly lower than for VIP and for the reference agonist, isoprenaline in both layers. Atriopeptin II was equally efficient in relaxing the K+‐depolarized anda1‐‐contracted longitudinal segments. Neither theβ‐antagonist, propranolol nor the guanylate cyclase inhibitor, methylene blue, modified the potency or the intrinsic activity of AP II. These results suggest that concentrations of circulating atriopeptins above 10 nM may contribute to reduction of vascular tone by the methylene blue insensitive receptors for AP II and III in the portal‐mesenteric vein region.
Effect of neuroactive agents on cholecystokinin release from the isolated, perfused porcine duodenum
Authors: CANTOR P. , HOLST J. J. , KNUHTSEN S. , REHFELD J. F.
Published: December 2008

Effect of neuroactive agents on cholecystokinin release from the isolated, perfused porcine duodenum. Acta Physiol Scand130, 627–632. Received 26 April 1986, accepted 8 March 1987, ISSN 0001–6772. Departments of Clinical Chemistry and Surgery C, Rigshospitalet, and Institute of Medical Physiology C, The Panum Institute, University of Copenhagen, Denmark.

To elucidate the mechanisms involved in the regulation of CCK release from the small intestine, the effect of neuroactive agents on the release of CCK from the isolated, perfused porcine duodenum has been studied. CCK in the venous effluent was measured by three radio‐immunoassays specific for the N‐terminus, the tyrosin‐o‐sulphated region and the C‐terminus of CCK‐33. Gastrin‐releasing peptide (GRP) at concentrations of 10‐‐10 and 10‐‐9 M in the arterial line increased the CCK output by about 100 and 500%, respectively, as measured with the assay specific for the sulphated region of CCK. Pilocarpine and physostigmine at concentrations of 10‐‐5 m reduced the CCK output to 24 and 40% of basal, respectively, and also abolised the GRP‐stimulated CCK response. Atropine (10‐‐6 M) increased CCK output about 100%. The results suggest that both stimulatory and inhibitory nervous impulses may be transmitted to the intestinal CCK cell, mediated by intramural GRP neurons and cholinergic pathways, respectively.
Adrenal function of the rat in relation to peroral administration of xylitol: depression of aldosterone
Authors: HÄMÄLÄINEN M. M. , MÄKINEN K. K.
Published: December 2008

Adrenal function of the rat in relation to peroral administration of xylitol: depression of aldosterone.Acta Physiol Scand130, 687–693. Received I September, 1986, accepted 10 March 1987. ISSN 0001–6772. Department of Biochemistry, Institute of Dentistry, University of Turku, Finland, and School of Dentistry, The University of Michigan, Ann Arbor, Michigan, USA.

The effect of peroral administration of xylitol (5% or 20% in food) on adrenal function was investigated in thirty‐five Long‐Evans male rats. The control rats were fed either a non‐substituted stock diet or a 20% glucose diet. Glucose elevated and 20% xylitol reduced the growth of the rats (P0.001), but 5% xylitol had no effect on the body weight. The concentrations of serum glucose and lactic acid decreased in rats fed 20% and 5% xylitol, respectively, but those of insulin, glucagon, corticosterone and aldosterone were not affected. In the adrenal glands, 20% xylitol loading was associated with increased epinephrine (P0.05) and norepinephrine (P0.001), but with decreased aldosterone (P0.001) concentrations. The weights and histological picture of adrenal glands were normal. The urinary pH of xylitol‐fed rats decreased significantly (P0.01). Although peroral xylitol affected the levels of aldosterone and catechola‐mines, a normal glucocorticoid metabolism was permitted. The reduced aldosterone levels were regarded as secondary reactions, possibly resulting from alterations in electrolyte and/or acid‐base balance. The increased catecholamine synthesis may be associated with the promoting effect of xylitol on intestinal calcium absorption.
On the nature of endogenous purines modulating cholinergic neurotransmission in the guinea‐pig ileum
Authors: WIKLUND N. P. , GUSTAFSSON L. E.
Published: December 2008

By means of agonist and enzyme experiments, the relative importance of endogenous adenosine, adenine nucleotides or other purines as modulators of cholinergic neuroeffector transmission in preparations of guinea‐pig ileum muscle has been examined. Adenosine, 2‐chloroadenosine, AMP, ADP, ATP and AMPPNP reversibly inhibited contractile responses to transmural stimulation of the guinea‐pig ileum longitudinal muscle. 5′‐adenylate deaminase dose‐dependently antagonized the inhibitory effect of adenosine, AMP, ADP, ATP and AMPPNP, but not that of 2‐chloroadenosine. 8‐p‐sulphophenyltheophylline, adenosine deaminase and 5′‐adenylate deaminase enhanced contractile responses to transmural nerve stimulation. Adenosine deaminase and 5′‐adenylate deaminase were virtually equiactive whereas 8‐p‐sulphophenyltheophylline was much more effective, and the theophylline derivative also enhanced contractile responses in preparations pretreated with adenosine deaminase or 5′‐adenylate deaminase. Moreover, 8‐p‐sulphophenyltheophylline abolished the inhibition by dipyridamole, whereas adenosine deaminase and 5′‐adenylate deaminase only partly antagonized the inhibitory effect of dipyridamole. Application of 5′‐adenylate deaminase did not enhance the nerve‐induced contractions in preparations pretreated with adenosine deaminase or a combination of dipyridamole and adenosine deaminase.

In conclusion, adenosine deaminase and 5′‐adenylate deaminase enhanced the nerve‐induced contractions in the ileum, and, since 5′‐adenylate deaminase was inactive after pretreatment with adenosine deaminase, this suggests that endogenous adenosine rather than 5′‐adenine nucleotides modulated cholinergic neurotransmission in the ileum. However, the adenosine receptor antagonist 8‐p‐sulphophenyltheophylline was much more effecctive than the enzymes, suggesting that endogenous purines other than both adenosine pr classical 5′‐adenine nucleotides were involved in the purine modulation of neurotransmission in ileum muscle.
Vago‐vagal activation of naloxone‐sensitive non‐adrenergic, non‐cholinergic jejunal contractions in the anaesthetized cat
Authors: GUSTAFSSON B. , DELBRO D.
Published: December 2008

Experiments were performed on chloralose‐anaesthetized cats, pretreated with guanethidine and with ligated adrenals and sectioned splanchnic nerves. The animals were paralysed and artificially ventilated. Jejunal motility was recorded by an intraluminal balloon, as volume changes at a constant pressure. Cervical or abdominal vagal afferent stimulation was performed before and after the administration of atropine. In both circumstances jejunal contractions were elicited. The latency of onset and the duration of the responses were significantly shorter before than after atropine. Strength‐duration and frequency‐response relationships, respectively, did not differ significantly prior and subsequent to atropine. Naloxone (0.05–0.5 mg kg‐1i.v.) blocked these reflexly induced atropine‐resistant jejunal contractions, as did section of the contralateral vagus. Possible mechanisms of action of these putative opioid receptor‐mediated neurogenic effects are discussed. The present study demonstrates that nonadrenergic, non‐cholinergic, naloxone‐sensitive jejunal contractions can be elicited as a vago‐vagal reflex, where the receptive field seems to be located within the abdominal cavity.
The effect of progesterone and its metabolites on the interictal epileptiform discharge in the cat's cerebral cortex
Authors: LANDGREN S. , AASLY J. , BÄCKSTRÖM T. , DUBROVSKY B. , DANIELSSON E.
Published: December 2008

The antiepileptic effect of progesterone, 5‐α‐pregnane‐3,20‐dione, 3‐α‐hydroxy‐5‐α‐pregnane‐20‐one, and 3‐α‐hydroxy‐5‐β‐pregnane‐20‐one were tested in an experimental animal model, and compared with the effect of clonazepam. The steroids were dissolved in serum from ovariectomized cats. Ovariectomized adult cats were used and spontaneous epileptic discharges were generated by placing small pieces of penicillin‐soaked filter papers on the ipsi and contralateral cerebral cortex. The frequency and amplitude of the interictal epileptiform spikes were recorded, and analysed in a computer. The changes in frequency and amplitudes were calculated. The drugs were infused during 20‐s periods into one cerebral hemisphere via the ipsilateral lingual artery with speeds of 1.1, 3.4 and 6.3 ml min‐1. A penicillin focus on the contralateral hemisphere served as a simultaneous control. Progesterone and clonazepam showed similar inhibitory effects on epileptiform interictal spiking (median reduction of spike frequency 21%, cf. Table I). The 5‐α‐pregnane‐3, 20‐dione was generally less potent than progesterone (median reduction 9%) and the 5‐α‐ and 5‐β‐pregnanolones were two to three times more potent than progesterone (54–66% reduction). The latency of the inhibitory effect was 4–10 s measured from the entrance of the infusion into the lingual artery. The depression lasted 10–20 min. It is concluded that the pregnanolones have strong antiepileptic properties. The rapid onset of effect indicates that the steroids may interact with the neuronal function at the membrane or synaptic levels.
The effect of prostaglandin synthesis inhibition on motility of the sheep ureter
Authors: THULESIUS O. , ANGELO‐KHATTAR M. , ALI M.
Published: December 2008

To determine the effect of prostaglandin‐synthesis inhibition on ureteral motility, isolated rings of sheep ureters were suspended for recording isometric tension in organ baths filled with Krebs‐Henseleit solution. The non‐steroidal anti‐inflammatory drugs (NSAIDs) indomethacin and diclofenac sodium (10–5M) inhibited rhythmic ureteral motility by reducing frequency, amplitude and finally stopping contractions. Prostaglandin F2α, 6‐keto‐prostaglandin F1αand thromboxane B2were determined by radio‐immunoassay in the bathing solution before and after addition of NSAIDs. Peak contractile activity at loo min of suspension was associated with increased concentration of all three prostanoids and 50 min after addition of indomethacin and diclofenac sodium when rhythmic contractions stopped, concentration dropped to low levels. The concentration of prostaglandins released into the organ bath were not quantitatively related to the frequency of contractions and therefore do not seem to affect pacemaker activity within ureteral smooth muscle but rather intercellular recruitment of myogenically active fibres. These findings indicate that prostaglandins play a role in the motor control of the ureter, and that non‐steroidal anti‐inflammatory drugs exert an inhibitory action.
Ultrastructure of pancreatic duct cells at secretory rest and during secretin‐dependent NaHCO3 secretion
Authors: BUANES T. , GROTMOL T. , LANDSVERK T. , RÆDER M. G.
Published: December 2008

The study was undertaken to identify possible ultrastructural changes occurring in pancreatic duct cells in relation to secretin‐dependent NaHCO3 secretion, Pancreatic biopsies were obtained for examination, following in situ glutaraldehyde fixation from four groups of anaesthetized, young pigs. In the resting state, pancreatic duct cell cytoplasm was found to contain multiple vesicles of approximately 0.2 μm diameter. Elevation of systemic arterial PCO2 to 11.1 (10.6–11.6) kPa increased the number of vesicles per unit volume of resting cells by approximately 250%. During secretindependent NaHCO3 secretion, the duct cell cytoplasm was devoid of vesicles. Following cessation of secretin‐dependent NaHCO3 secretion, cytoplasmic vesicles reappeared. The observed changes in the population of cytoplasmic vesicles in pancreatic duct cells may be causally related to the exocrine secretion of NaHCO3.
Effects of subacute toluene exposure on protein phosphorylation levels in rat frontoparietal and striatal membranes
Authors: VON EULER G. , FUXE K. , HANSSON T. , BENFENATI F. , AGNATI L. F. , GUSTAFSSON J.‐Å.
Published: December 2008

Effects of subacute toluene exposure (80 p.p.m. toluene in air, 5 + 4 days, 6 h day‐1) were analysed on calcium (Ca2+)‐ and cyclic adenosine monophosphate (cAMP)‐induced protein phosphorylation levels in membrane preparations from the frontoparietal cortex and the striatum of the adult male rat. After protein separation by gel electrophoresis, the amount of radioactive phosphate incorporated from adenosine 5′‐[γ‐32P] triphosphate, tetra‐(ethylammonium) salt ([32P]ATP) was measured indirectly by auto‐radiography. The 21 most phosphorylated protein bands were then analysed by computerized image analysis. In the frontoparietal cortex no protein bands were significantly affected after cAMP‐induced back phosphorylation, while after Ca2+ stimulation there was a decreased incorporation of [32P]ATP in a 22,000 protein band. In the striatum there was a reduced incorporation of [32P]ATP in a 26,000 protein band after cAMP‐induced back phosphorylation, and in four bands of 20,000, 21,000, 52,000 and 134,000, respectively, after Ca2+ stimulation. The reduced incorporation of [32P]ATP in these proteins indicated increased original phosphorylation levels after toluene exposure. A comparison between the frontoparietal cortex and the striatum showed a selective vulnerability of phosphorylation processes in striatal membrane protein bands. In conclusion, toluene exposure at low doses augments membrane protein phosphorylation levels in the rat forebrain and especially in the striatum, probably leading to changes in information handling and/or metabolic changes.
Qualitative characteristics of the mechanical response in rat papillary muscles to increase in extracellular calcium concentration
Authors: SKOMEDAL T. , SCHIANDER I. , AASS H. , OSNES J.‐B.
Published: December 2008

The qualitative characteristics of the inotropic response to increase in extracellular calcium (Ca0) were studied in isolated, electrically driven, isometrically contracting rat papillary muscles. All experiments were done in the presence of adrenergic receptor blockers. Ca0was increased in a cumulative way by exchanging a small fraction of the incubation solution with a corresponding solution with higher calcium concentration (8 mmol 1–1). At any Ca0level there was an almost proportional increase in parameters describing different parts of the contraction‐relaxation cycle as compared with results at the preceding lower Ca0level. Time to peak tension was prolonged at high compared with low Ca0levels. The response to increased Ca0was very similar to the cyclic AMP (cAMP)‐independent inotropic response elicited through activation ofα‐adrenergic receptors (α‐type response, Skomedalet al. 1982) and strikingly different from the cAMP‐dependent inotropic response elicited, for example, through activation ofβ‐adrenergic receptors (β‐type response, Skomedalet al. 1982). As the inotropic response to increased Ca0is known to be cAMP‐independent (Döngeset al. 1977), the present results demonstrate the interrelationship between the regulatory function(s) and the direct effector function(s) of calcium in the myocardium.
A microcalorimetric study of the sodium‐potassium‐pump and thermogenesis in human skeletal muscle
Authors: FAGHER B. , SJÖGREN A. , MONTI M.
Published: December 2008

Thermogenesis in human skeletal muscle was monitored by measurement of heat production using perfusion microcalorimetry. Heat production significantly correlated with relative body weight. The energy expenditure of the Na–K‐pump (ΔP), assessed after inhibition by ouabain in Krebs‐Ringer phosphate buffer containing glucose and insulin, amounted to 6% of the total heat production in vastus lateralis muscle. Muscle potassium positively correlated with ΔP (r= 0.84,P< 0.005). For rectus abdominis muscle ΔP was 8–15%; 95% confidence interval for the difference was 3–5% when comparison was made with vastus lateralis. The finding of a positive relationship between ΔP and muscle magnesium (r= 0.68,P< 0.04) is possibly explained by the dependence of ATP hydrolysis on internal magnesium. Our data on resting thermogenesis in small muscle samples agree to previous estimates of O2consumption in human skeletal musclein vivo.
Bicarbonate secretion by the rabbit duodenumin vivo:effects of prostaglandins, vagal stimulation and some drugs
Authors: GRANSTAM S.‐O. , FLEMSTRÖM G. , NYLANDER O.
Published: December 2008

Duodenal HCO3‐secretion in anaesthetized rabbits was measured by continuous titration of the recirculating luminal perfusate at pH 7.4. The segment under study started 3–4 cm distal to the pylorus and was devoid of pancreatic and biliary HCO3‐secretion. On histological examination the submucosa was seen to contain Brunner's glands, mainly of a mucous type. Duodenum in rabbit secreted HCO3‐at a considerably higher basal rate (100–125μequiv h‐1cm‐1of intestine) than has previously been found in the rat, cat or dog. The cyclo‐oxygenase inhibitor indomethacin (20 mg kg‐1) reduced the secretion by 30%, while prostaglandin E2(5–80μm, luminal) caused a dose‐dependent increase. Prostaglandins thus seem to be important in regulation of duodenal HCO3‐secretion in the rabbit and may play a role in duodenal protection against acid. Carbachol (1 and 10μg kg‐1) and atropine (0.5 and 1 mg kg‐1) had no effects whereas hexamethonium (to mg kg‐1) caused a persistent decrease (25%) in secretion. Effects of electrical stimulation of the vagal nerves or injection of the alpha2‐adrenergic agonist clonidine markedly depended on the agent used for anaesthesia. In urethane‐anaesthetized animals, clonidine (0.75–75μg kg‐1) tended to increase the secretion whereas with nembutal, clonidine (5–150μg kg‐1) decreased it significantly. Electrical stimulation of the cervical vagal nerves decreased the HCO3‐secretion in urethane‐anaesthetized animals but had no significant effect during nembutal anaesthesia. The responses in the nembutal‐anaesthetized rabbit are similar to those previously observed in the cat, rat or dog.
Fluid and protein fluxes across small and large pores in the microvasculature. Application of two‐pore equations
Authors: RIPPE B. , HARALDSSON B.
Published: December 2008

Treating the blood–tissue barrier as a two‐pore membrane the separate fluid and solute fluxes occurring across ‘small pores’ and ‘large pores’ were modelled in continuous capillaries employing two‐pore equations for the calculations together with the non‐linear flux equation and theories for restricted diffusion and for the reflection coefficient (s̀). The two‐pore equations derived proved useful for analyses of transvascular protein flux data obtained at low as well as at high filtration rates. These equations were applied ro lymphatic protein flux data from dog paw (Renkin et al. 1977 a, b) and to tracer albumin uptake data from rat skeletal muscle (Rippe et al. 1979). For both sets of data the small‐ and large‐pore radii became closely similar, 44 vs. 45 Å and 240 vs. 225 Å, which also holds for the large‐pore fractions of hydraulic conductivity (0.097 vs. 0.056). The main result of this analysis is that the passage of macromolecules normally occurring across the microvascular walls is almost entirely convective, and hence, dependent on the transmural hydrostatic and oncotic pressure gradients and on the hydraulic conductivity. For example, 75–90% of the transvascular passage of albumin was found to be due to convection through large pores at normal lymph flows, the remaining portion being mainly due to diffusion across small pores. Solutes larger than albumin were almost exclusively transported by convection across large pores. Two‐pore heterogeneity was found to explain the previously observed variations of the apparent overall large solute diffusion capacity (PSapp) and the overall reflection coefficient (s̀1) with filtration rate and also previous overestimations of PS. Furthermore, the present results were not compatible with protein transport across any ‘non‐hydraulically conductive capillary pathways’ as previously postulated from the lymphatic protein flux data analysed here (Renkin 1985).
Functionalα‐adrenoceptors in human atrial preparations in the presence ofβ‐receptor blockade
Authors: ASK J. A. , STENE‐LARSEN G. , HELLE K. B. , RESCH F.
Published: December 2008

Inotropic effects via cardiacα‐adrenoceptors were studied in electrically driven auricular strips (1 Hz, 37 °C) from patients treated withβ‐blockers for months prior to open heart surgery. Markedα‐mediated positive inotropic effects were demonstrated with adrenaline (A), noradrenaline (NA) and phenylephrine (PHE) in the presence ofβ‐blocker and with blockers of the muscarinic receptor and of the neuronal and extraneuronal uptake mechanisms for the catecholamines. In the presence of ± 10‐6mpropranolol the maximal effects as well as the potencies (pD2‐values) for A and NA were not significantly different while higher than for PHE. Theα1‐blocker, prazosin (10‐6m), markedly reduced the pD2values but not the intrinsic activities (α‐values) for A, NA and PHE in theβ‐blocked preparations. Methoxamine, however, induced negative inotropic responses at normal and low frequencies (1, 0.5 and 0.1 Hz) of stimulation, suggestive of non‐specific, cardiodepressant effects. Other agonists withα‐effects in other types of tissue (oxymethazoline, xylomethazoline and clonidine) were without effects on the force and velocity of contraction in the auricular strips under the present experimental conditions.

The results showα1‐type of adrenoceptor‐induced inotropic effects for A, NA and PHE duringβ‐blockade in human auricular strips, indicating that cardiacα1‐receptors may have clinical importance by increasing the inotropy of the human myocardium treated withβ‐blocking agents.
Catecholamine‐induced free radicals in myocardial cell necrosis on experimental stress in pigs
Authors: HÄGGENDAL J. , JÖNSSON L. , JÖHANSSON G. , BJURSTRÖM S. , CARLSTEN J. , THORÉN‐TOLLING K.
Published: December 2008

Normal pigs, crossbreeds of Swedish Landrace and Yorkshire, about 6 months old, were subjected to experimental stress, induced by the myorelaxant succinylcholine, for 12 min. Besides one group of control pigs, one group of pigs were pretreated with atocopherol (vitamin E) combined with selenium (Tokosel Vet®) injected i.m. every second day for 11 days, and another group was given zinc (ZnSO4.7H2O) in the fodder for 1 month plus one injection i.p. 2 days before the stress. The stress‐induced heart lesions, morphologically graded according to evaluation scores, were significantly reduced in both the pretreated groups when compared with the control pigs. The blood levels of catecholamines (CA) were increased to about the same degree in the three groups during the stress. The protection observed is suggested to be due to the fact that vitamin E, selenium and zinc are involved in systems acting as scavengers of free radicals. The present results together with earlier ones are discussed to support the CA‐hypothesis for stress‐induced heart lesions: some types of stress can increase the sympathetic activity to such an extent that released CA, viaβ‐adrenoceptor mechanisms affects the cell metabolism to such a degree that cytotoxic free radicals are formed, producing myocardial cell necrosis.
Pentylenetetrazol seizure threshold and extracellular levels of cortical amino acids in taurine‐deficient kittens
Authors: LEHMANN A.
Published: December 2008

Directly after weaning, kittens were raised on a semisynthetic diet supplemented with 0.4% taurine or devoid of this amino acid. Eight to twelve weeks later the blood plasma concentration of taurine was decreased by 98–99% in kittens fed a taurine‐free regimen. Parietal cortex dialysis, performed in anaesthetized kittens, revealed a selective, but less marked, reduction of extracellular taurine. When kainic acid was included in the dialysis buffer, taurine was doubled in taurine‐supplemented kittens, but it was only slightly affected in deficient animals. The animals were also used for determination of the threshold of pentylenetetrazol‐induced epilepsy J days after the dialysis experiment. This was not significantly different between the groups. The present work shows that taurine deficiency in its own right does not elevate interstitial glutamate, an effect previously observed in the z‐guanidino‐ethane sulphonic acid model for taurine deficiency. The results further suggest that taurine is better retained in neural cells in the taurine‐deficient state. Moreover, the findings argue against a role for endogenous taurine in the control of epileptiform discharge initiation and/or spread.
Release of neuropeptide Y upon haemorrhagic hypovolaemia in relation to vasoconstrictor effects in the pig
Authors: RUDEHILL A. , OLCÉN M. , SOLLEVI A. , HAMBERGER B. , LUNDBER J. M.
Published: December 2008

Neuropeptide Y is co‐stored with noradrenaline in peripheral sympathetic nerves, but is not present in the adrenal chromaffin cells in the pig. Plasma levels of neuropeptide Y‐like immunoreactivity and catecholamines were studied upon haemorrhagic shock in the anaesthetized pig. The animals were bled in two successive steps (30 and 10 ml kg–), resulting in a reduction of the mean arterial blood pressure by 44% and 53 %, respectively. Plasma levels of noradrenaline increased abruptly after the first bleeding from 1.21 ± 0.27 to 26.5 ± 6.3 nmol 1‐1. Plasma neuropeptide Y showed a progressive increase from 62 ± 8 pmol 1–1 in the basal state to 365 ± 98 pmol 1–1 at 60 min after the first bleeding. After the second bleeding plasma neuropeptide Y and noradrenaline showed a largely parallel increase and finally reached levels of 2524 ± 580 pmol 1–1 and 316 ± 117 nmol 1–1, respectively. A veno‐arterial gradient of neuropeptide Y and noradrenaline indicating local release was present over the spleen after both bleeding steps. The overflow of neuropeptide Y was delayed about 15 min compared to noradrenaline after the initial bleeding. Depletion of the neuropeptide Y content after shock in the heart and skeletal muscle supported local release also from these organs. Infusions of neuropeptide Y to obtain similar plasma concentrations as during shock (nM range) caused reduction in blood flow as determined by the radionuclide‐labelled microsphere technique in several organs including spleen and skeletal muscle (threshold response at 319 ± 22 pmol 1–1) but not in heart and brain. In conclusion, both neuropeptide Y and noradrenaline were markedly elevated in plasma upon haemorrhagic shock, suggesting release from sympathetic nerve terminals. Neuropeptide Y could therefore have a role as a sympathetic neurotransmitter, and during severe stress, circulating plasma levels are in the range where vasoconstriction is evoked by exogenous NPY.
Effects of adenosine on autonomic control of heart rate in man
Authors: CONRADSON T.‐B. G. , CLARKE B. , DIXON C. M. S. , DALTON R. N. , BARNES P. J.
Published: December 2008

Six healthy subjects (two female) aged 23–40 years participated in a double‐blind randomized cross‐over study to investigate autonomic mechanisms involved in the chronotropic effect of adenosine in conscious man. Adenosine was infused in increasing doses following saline, propranalol (0.2 mg kg‐1 body weight) or propranolol (0.2 mg kg‐1 plus atropine (0.04 mg kg‐1). Heart rate and blood pressure were measured supine, on standing and during a Valsalva manoeuvre. Plasma catecholamines were measured in the supine and standing positions. Following saline, adenosine (up to 120 μg kg‐1 min‐1) caused a dose‐related increase in heart rate (mean±SD maximum increase 18±8 bpm; P < 0.01). The change in heart rate with adenosine after propranolol (12±9 bpm; P < 0.05) did not differ significantly from the corresponding change following saline but was abolished by propranolol plus atropine, which, in turn, was associated with a mean maximum decrease in heart rate of 5±3 bpm (P < 0.01). The increase in heart rate during the initial 30 s on standing was augmented with adenosine compared with saline (16 ± 5 bpm; P < 0.01). A significant increase in plasma noradrenaline on standing was also found with adenosine compared with saline (6.37 ± 2.86 vs. 4.77 ± 1.79 nmol 1‐1; P < 0.05). The heart rate response to the Valsalva manoeuvre was not affected by adenosine. These results suggest that the positive chronotropic effect of infused adenosine in conscious man may in part be caused by an inhibition of cardiac vagal tone. An activation of sympathetic nerve activity may be contributary.
Respiratory and neuroendocrine responses of piglets to hypoxia during postnatal development
Authors: MOSS I. R. , RUNOLD M. , DAHLIN I. , FREDHOLM B. B. , NYBERG F. , LAGERCRANTZ H.
Published: December 2008

Breathing response to 12% and 6% O2in N, (at isocapnia) was measured in anaesthetized piglets, 1–5 and 19–25 days old, before and after 3 mg kg‐1i.v. naltrexone. The degree of interaction between the anaesthetic and naltrexone was assessed. At the end of each hypoxic trial, arterial blood was sampled for measurements of pH and gas tensions, (Met)enkephalin‐Arg5‐Phe7, adenosine, noradrenaline and adrenalin. Where‐as respiration in older animals was stimulated by hypoxia, young piglets had a biphasic response with a pronounced ventilatory decrease in response to severe hypoxia (6% O2/N2). In young animals there was a greater ventilatory response with naltrexone than without the drug, and the biphasic hypoxic response was ameliorated or reversed by naltrexone. Levels of adrenalin increased and those of encephalin, adenosine and noradrenaline tended to increase during hypoxia in the younger age group. Levels of adenosine showed significant increase when data from both age groups and levels of hypoxia were pooled. Combined with previously reported physiological evidence regarding adenosine in hypoxic depression, we conclude that the present results are compatible with a role of opioid peptides and adenosine in the early postnatal response to hypoxia.
α‐Adrenoceptor stimulation, but not muscarinic stimulation, increases cyclic AMP accumulation in brain slices due to protein kinase C mediated enhancement of adenosine receptor effects
Authors: FREDHOLM B. B. , LINDGREN E. , LINDSTRÖM K. , NORDSTEDT C.
Published: December 2008

In the present study, using rat hippocampal slices, we have further examined the stimulatory effect ofα1adrenoceptors on the accumulation of cyclic AMP, which is known to depend on calcium and adenosine. The addition of noradrenaline (NA) stimulated the accumulation of [3H]inositol phosphates in [3H]inositol‐treated slices. This effect was shared by carbachol (10–100μmol l‐1) but not by the adenosine receptor agonist 2‐chloroadenosine (100μmol l‐1). The stimulatory effect of theα‐agonists (phenylephrine or NA + propranolol) on cyclic AMP was shared by a diacylglycerol derivative,sn‐1‐oleyl‐2‐acetyl glycerol (OAG), and by the tumour‐promoting phorbol esters phorboldibutyrate (PDiBu) and tetradecanoyl phorbol acetate (TPA). PDiBu caused a translocation of protein kinase C from soluble to particulate fractions. The effects of PDiBu andα‐adrenoceptor stimulation on cyclic AMP were not additive. Surprisingly, carbachol (1–1000μmol l‐1) did not stimulate cyclic AMP accumulation in rat hippocampal slices either in the presence or in the absence of an adenosine receptor agonist.

The results are compatible with the opinion that a‐adrenoceptor stimulating drugs enhance the formation of inositol phosphates and diacylglycerol, which synergistically activate protein kinase C, which in turn augments the stimulation of cyclic AMP formation. Thus, a neurotransmitter whose principal biological effect is to stimulate inositol phosphate formation can influence cyclic AMP formation by virtue of an interaction with the actions of the ubiquitous neuromodulator adenosine. The fact that the effect of theα‐receptor stimulation was not mimicked by a muscarinic agonist could indicate that other factors besides activation of inositol phospholipid hydrolys are important for this receptor–receptor interaction.
Interaction of noradrenaline, NPY and VIP with the neurogenic cholinergic response of the rat uterine cervixin vitro
Authors: STJERNQUIST M. , OWMAN CH.
Published: December 2008

Quantitative pharmacological studies were performed on isolated uterine cervix which was obtained from oophorectomized and oestrogen‐treated rats and therefore showed no spontaneous contractility. The concentration‐response curves to ACh and carbacholine were to a varying degree depressed and right‐shifted in the presence of NA, but not NPY or VIP. The electrically induced cholinergic contraction was potentiated in tissues from animals pretreated with reserpine or 6‐OHDA, but only at high stimulation frequencies. Histochemically, both sympatholytics abolished NA from the cervical fibres, whereas immunoreactive NPY was still encountered. Tyramine in the organ bath reduced the contraction amplitude during electrical nerve stimulation concentration‐dependently by aβ‐adrenoceptor‐sensitive mechanism. In the presence of neostigmine the amplitude was reduced by NA, but not by NPY or VIP, which, on the other hand, had an inhibitory effect in the absence of neostigmine. The results offer further support for the view that, although the cervical smooth muscle cells are equipped with adrenoceptors, the neurogenic motor response at low stimulation frequencies (around 3 Hz) is mainly cholinergic. It appears that neurally released NA is able to influence these muscle cells primarily at high frequencies. There is no clear‐cut evidence that the inhibitory effects of neural NPY or VIP on the cervix of spayed, oestrogen‐treated rats are mediated by postjunctional receptors.
Influence of reduced muscle temperature on metabolism in type I and type II human muscle fibres during intensive exercise
Authors: BLOMSTRAND E. , ESSÉN‐GUSTAVSSON B.
Published: December 2008

Six male subjects performed intensive cycle exercise to exhaustion after cooling their legs in water at 10–12 °C (muscle temperature (Tm) 28±2.6 °C, mean ±SD). Exercise at exactly the same rate and duration (370±34 W, 1.5±0.2 min) was then repeated by each subject 2–5 weeks later at normal Tm (35 ± 1.0 °C). Muscle biopsies were taken from the vastus lateralis muscle at rest and after exercise. The muscle tissue was freeze‐dried and fragments of single fibres were dissected out. The fibres were classified and pooled into groups of type I and type II. Analyses of glycogen, glucose 6‐phosphate, lactate and phosphagens were performed on pools of type‐identified fibres.

After exercise at reduced Tm, all subjects had higher concentrations of glucose 6‐phosphate and lactate in both type I and type II fibres, and in most subjects the concentrations of ATP and phosphocreatine were lower as compared with the findings after exercise at normal Tm. During exercise the glycogen content of both fibre types decreased to a greater extent at reduced than at normal Tm in most subjects.

The results suggest that during intensive dynamic exercise at reduced. Tm there is a higher degree of glycolysis from glycogen in the muscle than in the normal situation. In some subjects the cause of fatigue may be related to a more rapid accumulation of lactate in the cold muscle, while in others fatigue may be related to alternative factors, e.g. low levels of ATP and phosphocreatine.
Transport of leucine, lysine, glycine and aspartate in neuroblastoma C1300 and glioma C6 cells
Authors: HANNUNIEMI R. , PAJARI‐BACKAS M. , OJA O. S. , OJA S. S.
Published: December 2008

Non‐saturable penetration and the V and Km constants of saturable influx of leucine, lysine and glycine were always greater in cultured neuroblastoma (C1300) than in glioma (C6) cells. Aspartate uptake was detected only in glioma cells. Unstimulated efflux of the amino acids was initially fast in both cell types but soon slowed down. The efflux of glycine and aspartate exhibited no heteroexchange, the efflux of lysine was stimulated by extracellular leucine and that of leucine slightly by lysine and glycine but only in glioma cells.
Mechanisms of stimulation of acid production in parietal cells isolated from the pig gastric mucosa
Authors: MÅRDH S. , SONG Y.‐H. , CARLSSON C. , BJÖRKMAN T.
Published: December 2008

Sequential incubations with pronase and collagenase of pig gastric mucosa resulted in single cell preparations containing 10–20% parietal cells, which could be enriched further to 85–95 % purity by density‐gradient centrifugation followed by elutriation. Acid production of the isolated cells was measured by means of aminopyrine accumulation in their acid compartments. When small pieces of the mucosa were pretreated for 1 h in the presence of either histamine, pentagastrin or carbachol before preparation of cells, the ability of the subsequently isolated cells to produce acid was increased. In parietal cells isolated from resting (not pretreated) mucosa pentagastrin, carbachol and also adrenaline increased the histamine‐stimulated aminopyrine accumulation (50–90 % increase). Adrenaline alone had no significant effect on the aminopyrine accumulation. In the presence of 10‐4mhistamine the apparent EC50for adrenaline was 5 × 10‐7m. Adrenaline, histamine, forskolin and isobutylmethylxanthin (IBMX) increased the formation of cAMP in purified parietal cells. The three ‘classical’ secretagogues histamine, pentagastrin and carbachol, but also IBMX and forskolin, increased the cytosolic free Ca2+from approximately 1.5 × 10‐7mto 2.2–3.5 × 10‐7mbut adrenaline and dibutyryl cyclic AMP did not. Thus the present results indicate that there are – in addition to histaminergic H2receptors – specific cholinergic, gastrinergic and adrenergic receptors on the plasma membrane and that there are separate cAMP and Ca2+‐dependent stimulatory pathways in the parietal cell.
Distribution of nicotinic cholinergic receptors in the rat tel‐ and diencephalon: a quantitative receptor autoradiographical study using [3H]‐acetylcholine, [α‐125l]bungarotoxin and [3H]nicotine
Authors: HÄRFSTRAND A. , ADEM A. , FUXE K. , AGNATI L. , ANDERSSON K. , NORDBERG A.
Published: December 2008

The topographical distribution of [α:‐12T]bungarotoxin [125I]BTX, [3H]nicotine ([3H]Nic), [3H]acetylcholine ([3H]ACh) (in the presence of atropine) binding in rat teland diencephalon was investigated using a quantitative receptor autoradiographical technique. With the [3H|ACh and [3H]Nic radioligands, a strong labelling was observed in various thalamic nuclei, including the medial habenula, a moderate labelling in different areas of the cortex cerebri, the nucleus caudatus putamen, the nucleus accumbens and tuberculum olfactorium and a uniform weak labelling in the hypothalamus. When the binding data for [3H]Nic were plotted against binding data for [3H]ACh in various brain nuclei, a significant correlation was obtained. Considering [125I]BTX, the strongest labelling was observed in the lateral mammillary nucleus and the hilus gyrus dentatus of the hippocampal formation. A weak labelling occurred in areas such as the nucleus causatus putamen, the thalamus and the cerebral cortex. No significant correlation was therefore obtained between the degree of [125I]BTX binding in various brain nuclei and the degree of binding observed with [3H]Nic or [3H]ACh. The present results underline the view that the high‐affinity |3H]Nic and [3H]ACh binding sites label the same cholinergic nicotinic receptor binding site, while [125I]BTX labels another subpopulation of nicotinic cholinergic receptors, predominantly found in discrete areas of the hypothalamus and the limbic cortex.