bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of nicotine on blood flow, oxygen consumption and glucose uptake in the canine small intestine
Authors: Grayson J. , Oyebola D.D.O. 
Published: July 2012

Resting blood flow, arterio‐venous glucose and oxygen (A‐V)O2 differences, glucose uptake and oxygen consumption by a segment of the upper jejunum were measured in anaesthetized dogs. Systemic arterial pressure was also measured.
The effect of nicotine infusion (25 μg kg−1 i.v., over 10 min) on these measurements was recorded in untreated dogs, in dogs treated with propranolol (0.5 mg kg−1) to produce β‐adrenoceptor blockade and in dogs after α1,‐adrenoceptor blockade with prazosin (0.2 mg kg−1).
Nicotine cause a significant pressor response during infusion and a hypotensive response during the post infusion period. Propranolol did not significantly affect these results. Jejunal blood flow increased in the first half of nicotine infusion in both the untreated and β‐blocked animals. Vascular resistance was reduced during nicotine infusion and the decrease persisted post infusion in the β‐blocked group.
In the untreated group (A‐V)O2 was significantly reduced during the first 5 min of nicotine infusion, thereafter it returned to control levels, then rose significantly above control level, post infusion. β‐Adrenoceptor blockade had little effect on these responses to nicotine. When oxygen consumption was calculated it was found that nicotine had little effect during or after infusion.
Nictine caused significant hyperglycaemia during and for about 1 h after infusion. Tissue release of glucose was occasionally observed following the infusion. β‐Adrenoceptor blockade reduced the hyperglycaemia caused by nicotine. β‐Blockade alone increased glucose uptake and nicotine caused a further three to four fold increase. Prazosin abolished the effects that were observed in the untreated and the α‐blocked animals.
The present findings, related to our previous observations on the effects of catecholamines on glucose uptake by the bowel, are consistent with the hypothesis that nicotine has its action on bowel glucose uptake or release through its well‐established action in releasing catecholamines and in activating β‐adrenoceptors. The responses are not related to oxygen utilization.
Electrophysiological actions of nicotine on substantia nigra single units
Authors: Clarke P.B.S. , Hommer D.W. , Pert A. , Skirboll L.R. 
Published: July 2012

Extracellular recordings of single unit activity were made in the substantia nigra (SN) of chloral hydrate‐anaesthetized rats.
Dopaminergic neurones of the pars compacta (SNC) were stimulated by (—)‐nicotine bitartrate (1.0 mg k−1) given subcutaneously (s.c.). This action was prevented by the secondary amine mecamylamine HCl (2.0 mg kg−1 i.v.) but not by a ganglion‐blocking dose of the bisquaternary compound chlorisondamine Cl (0.1 mg kg−1 i.v.). Mecamylamine reduced the spontaneous activity of dopaminergic neurones.
Nicotine, when administered intravenously (2–128 μg kg−1 cumulative dose), also stimulated dopamine cells and this action was dose‐related.
Nicotine, administered intravenously, (2–128 μg kg−1 cumulative dose) markedly excited non‐dopamine cells in the pars reticulata (SNR) in a dose‐related manner. In rats pretreated with chlorisondamine (0.1 mg kg−1 i.v.), nicotine induced a small excitatory or depressant action, but the marked excitation was not seen. Mecamylamine (2 mg kg−1 i.v.) completely prevented the actions of nicotine.
The results are consistent with a direct excitatory action of nicotine on dopaminergic neurones of the substantia nigra pars compacta. The pronounced excitatory action of systemically administered nicotine on non‐dopamine cells of the pars reticulata appears to be of peripheral origin.
Excitatory effect of Clostridium perfringens alpha toxin on the rat isolated aorta
Authors: Fujii Yoshio , Nomura Shigemasa , Oshita Yoshitami , Sakurai Jun 
Published: July 2012

Clostridium perfringens alpha toxin caused contraction of the isolated aorta of the rat in a dose‐dependent manner.
The contractile action caused by the toxin was inhibited or abolished by calcium antagonists such as nifedipine, verapamil and cinnarizine, or a Ca‐free medium, but was not affected by phentolamine, chlorpheniramine, atropine, tetrodotoxin or a low Na medium.
The toxin stimulated Ca uptake into the aorta in a dose‐dependent manner.
8‐N,N'‐diethylaminooctyl‐3,4,5‐trimethoxybenzoate (TMB‐8) blocked significantly both the toxin‐ and noradrenaline (NA)‐induced contractions.
Trifluoperazine (TFP) and N‐(6‐aminohexyl)‐5‐chloro‐l‐naphtharene sulphonamide (W‐7) did not affect the contractile activity of the toxin but blocked the NA‐induced contraction.
The toxin also stimulated the 32P phosphate labelling of phosphatidylinositol (PI) and phosphatidic acid (PA) in the preparation.
These results indicate that the toxin‐induced contraction, which is different from that induced by NA, is the result of a direct action of the toxin on the aorta and is due to an increased Ca2+ permeability across the smooth muscle membrane. It is suggested that the contractile response to the toxin is associated with activation of phospholipid metabolism and enhanced entry of Ca into the aorta.
Urinary kallikrein excretion during inhibition of endogenous angiotensin II in the pig
Authors: Binder Bernd R. , Maier Manfred , Rana Hemanta , Starlinger Michael , Zhegu Zydi 
Published: July 2012

This study was performed to assess the possible contribution of endogenous angiotensin II (AII) to the regulation of urinary kallikrein excretion. The AII antagonist saralasin or the saline vehicle was infused into the aorta above the renal arteries of pigs under halothane‐O2/N2O anaesthesia. Systemic and renal functional parameters were followed for 140 min and during stimulation of the renin‐angiotensin system by haemorrhage.
Urinary kallikrein excretion, determined as kininogenase activity, was increased immediately upon both initiation and termination of the 2 h saralasin infusion into pigs not subjected to haemorrhage. Renal cortical blood flow (RCBF) was maintained in both saline and saralasin‐treated animals at blood pressures as low as 70 mm Hg, while glomerular filtration rate was dissociated during saralasin infusion. As long as RCBF was maintained, urinary kallikrein excretion rate was elevated during the progressive hypotension in both saline and saralasin‐treated animals.
These findings confirm a close relationship between the maintenance of RCBF and increased activity of the kallikrein‐kinin system whether or not AII is antagonized, and indicate that during haemorrhage the kallikrein‐kinin system is stimulated by a mechanism not involving AII.
Binding to serum α1‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation
Authors: Belpaire F.M. , Bogaert M.G. , Mugabo P. , Rosseel M.T. 
Published: July 2012

The β‐blocking effect of 4 β‐adrenoceptor antagonists with different pharmacokinetic properties was studied after intravenous and intraportal administration to control rats and to rats with experimental inflammation.
In rats with inflammation the effects of propranolol and oxprenolol, which are mainly bound to α‐acid glycoprotein (α1‐AGP), were significantly less after intravenous administration, but not after intraportal administration. In contrast, for metoprolol and atenolol, which are only negligibly serum bound, no difference was observed between control rats and rats with inflammation for either route of administration.
Total and unbound serum concentrations of propranolol were measured 20 min after intravenous and intraportal administration.
After intravenous administration, in the rats with inflammation total concentrations of propranolol were more than twice, and unbound concentrations less than half those of control rats. After intraportal administration the total concentrations were 8 times, and the unbound concentrations 3 times higher in the rats with inflammation.
There was a significant correlation between the β‐blocking effect and the unbound concentrations of propranolol after intravenous administration, but not after intraportal administration. The latter finding is probably because the unbound concentrations were supramaximal.
The effects of locally applied capsaicin on conduction in cutaneous nerves in four mammalian species
Authors: Baranowski Richard , Lynn Bruce , Pini Adrian 
Published: July 2012

By examination of compound action potentials in the saphenous nerve of the anaesthetized rat it has been shown that capsaicin causes a rapid, dose‐dependent, failure of conduction in many C‐fibres when applied directly to the nerve. A large reduction in C‐fibre conduction occurs with concentrations as low as 110 μM. After a 15–30 min exposure to capsaicin, only partial recovery occurs in 1 h.
Similar block of C‐fibre conduction occurs in the ferret. However, only smaller, reversible, reductions in C‐fibre conduction were seen in the guinea‐pig and rabbit, even at the highest concentration of capsaicin used (33 mM).
A small reduction in the Aδ component of the compound action potential occurred in all four species. In the rat and ferret the effects were much less than those on C‐fibres.
At high doses, small reversible effects were also seen on the fastest conducting Aαβ component of the compound action potential in the rat, rabbit and guinea‐pig; no effects were seen on the Aαβ fibres in the ferret.
Decreases in amplitude of the compound action potential were accompanied by some slowing of conduction in most cases. The slowing was less than 5% except for the rat Aαβ and C‐fibres and the ferret C‐fibres where 9–15% changes occurred at the highest doses of capsaicin.
Opening the connective tissue sheath of the nerve did not significantly increase the effectiveness of capsaicin.
Pressure reversal of alphaxalone/alphadolone and methohexitone in tadpoles: evidence for different molecular sites for general anaesthesia
Authors: Halsey Michael J. , Wardley‐Smith Bridget , Wood Steven 
Published: July 2012

Tadpoles were used to study quantitative interactions between high pressure and two intravenous anaesthetics, alphaxalone/alphadolone and methohexitone.
The potencies of the two agents were decreased by high pressure but to different extents. The maximum effect was seen in the pressure range 70–130 atmospheres absolute (ATA). The increases in the normobaric anaesthetizing concentration (ED50) required at 100 ATA were alphaxalone/alphadolone:405 ± 5 (s.d.)%; methohexitone:658 ± 80 (s.d.)%.
For both alphaxalone/alphadalone and methohexitone, the curves obtained when the increase in ED50 was plotted against increasing pressure showed plateaux at pressures above 70 ATA.
These data support the concept of the two intravenous drugs causing general anaesthesia by the occupation of separate molecular ‘sites’ with different but finite capacities.
The effect of α2‐adrenoceptor agonists on the acid secretory responses of rat isolated gastric mucosa to electrical field stimulation
Authors: Dettmar P.W. , Lord J.A.H. 
Published: July 2012

The effects of clonidine, UK‐14,304, noradrenaline, para‐aminoclonidine and phenylephrine were examined on the acid secretory response of the rat isolated gastric mucosa preparation to electrical field stimulation.
Clonidine, UK‐14,304, noradrenaline and para‐aminoclonidine but not phenylephrine (10 μM) reduced the response of the gastric mucosa stimulated at 2.5 Hz; gastric mucosae stimulated at higher frequencies were insensitive to the action of these α2‐adrenoceptor agonists.
The inhibitory effect of the selective α2‐adrenoceptor agonist UK‐14,304 was antagonized by idazoxan but not by prazosin.
These findings indicate that clonidine and other α2‐adrenoceptor agents inhibit the acid secretory response of the rat gastric mucosa to electrical field stimulation by an action at α2‐adrenoceptors, which are probably located on cholinergic nerve terminals.
Inhibition of calcium channels by harmaline and other harmala alkaloids in vascular and intestinal smooth muscles
Authors: Karaki H. , Kishimoto T. , Ozaki H. , Sakata K. , Umeno H. , Urakawa N. 
Published: July 2012

Effects of harmaline and other harmala alkaloids on the contractions induced in the vascular smooth muscle of rabbit aorta and intestinal smooth muscle of taenia isolated from guinea‐pig caecum were examined.
In rabbit isolated aorta, harmaline inhibited the sustained contraction induced by 65.4 mM K+ with an IC50 (concentration needed for 50% inhibition) of 4.6 × 10−5 M. This inhibitory effect on high K+‐induced contraction was antagonized by raising the concentration of external Ca2+ but not by Bay K 8644, a Ca2+ channel facilitator. Harmaline also inhibited the sustained contraction induced by noradrenaline (10−6 M) with an IC50 of 7.6 × 10−5 M. The inhibitory effects on noradrenaline‐induced contractions were not antagonized by raising the external Ca2+ concentrations or by Bay K 8644.
In guinea‐pig taenia, harmaline inhibited the 45.4 mM K+‐induced contraction with an IC50 of 6.8 × 10−5 M and the carbachol (10−6 M)‐induced contraction with an IC50 of 7.0 × 10−5 M. The inhibitory effects on both high K+‐ and carbachol‐induced contractions were antagonized by raising the external Ca2+ concentrations but not by Bay K 8644.
Harmaline, at the concentrations needed to inhibit the muscle contraction, inhibited the increase in 45Ca2+ uptake induced by high K+, noradrenaline and carbachol in aorta and taenia.
Harmaline did not change the cellular Na+ and ATP contents in resting and high K+ stimulated taenia.
Other harmala alkaloids also inhibited the contractions in these smooth muscles. The order of the inhibitory potency was 6‐methoxyharman = harmine > harmaline = 2‐methylharmine = harmane > 6‐methoxyharmalan > harmalol = harmol for the contractions induced by high K+ in aorta and taenia and by carbachol in taenia, and 2‐methylharmine > 6‐methoxyharman > 6‐methoxyharmalan = harmol = harmalol = harmane > harmine > harmaline for the contraction induced by noradrenaline in aorta.
These results suggest that harmaline inhibits the contractile response of rabbit aorta and guinea‐pig taenia by inhibiting different types of Ca2+ channel. The structure‐activity relationship indicates that the potency and selectivity of the inhibitory effects on these channels are varied by modification of the structure of this alkaloid.
The effects of noradrenaline, B‐HT 920, methoxamine, angiotensin II and vasopressin on mean circulatory filling pressure in conscious rats
Authors: Pang C.C.Y. , Tabrizchi R. 
Published: July 2012

The effects of vasoactive substances on mean circulatory filling pressure (MCFP), an index of total body venous tone, were determined in conscious rats.
Cumulative doses of saline (0.9% w/v NaCl solution), methoxamine (α1‐adrenoceptor agonist), B‐HT 920 (α2‐adrenoceptor agonist) noradrenaline and vasopressin, and individual doses of angiotensin II (AII), were infused into the rats. Mean arterial pressure (MAP), MCFP and heart rate (HR) were determined before and during the plateau responses to infusions of the vasoactive substances.
The infusions of all the agonists caused a dose‐dependent increase in MAP and a decrease in HR. The infusion of saline affected neither MAP nor HR.
The infusions of saline and methoxamine did not affect MCFP while the infusions of B‐HT 920, noradrenaline and AII increased MCFP. MCFP was slightly increased during the infusion of high doses of vasopressin.
It was concluded that receptors for the α2‐adrenoceptor agonist and AII are involved in the control of venous tone. Receptors for the α1‐adrenoceptor agonist and vasopressin are not important for the control of venous tone.
The effects of epithelium removal on the sensitivity of guinea‐pig isolated trachealis to bronchodilator drugs
Authors: Farmer S.G. , Fedan J.S. , Hay D.W.P. , Raeburn D. 
Published: July 2012

Mechanical removal of the epithelium increased the sensitivity of tracheal strips to isoprenaline, sodium nitroprusside, and to adenosine (only in the presence of inhibitors of its uptake and metabolism). Epithelium removal was without effect on sensitivity to salbutamol or papaverine.
Preincubation of tracheal strips with an inhibitor of extraneuronal uptake, corticosterone (50 μM), had no effect on tissue sensitivity to either salbutamol or papaverine. However, the steroid both increased sensitivity to isoprenaline, and abolished the effect of epithelium removal on sensitivity to this catecholamine.
These results suggest that in the guinea‐pig, the tracheal epithelium is a major source of extraneuronal uptake for catecholamines. Furthermore, the increase in trachealis sensitivity to isoprenaline following epithelium removal is probably due to loss of these sites of extraneuronal uptake.
The fact that sensitivity to salbutamol, papaverine and adenosine (in the absence of metabolic inhibitors) was not increased by denuding the epithelium indicates that loss of a diffusion barrier to drugs is not the mechanism of increased sensitivity.
Adenosine (and possibly nitroprusside) may cause the epithelium to release a smooth muscle excitatory factor. Thus, removal of the epithelium attenuates this excitatory influence and enhances smooth muscle responsiveness to adenosine.
These results provide further evidence that the epithelium has an important role in modulating the sensitivity of guinea‐pig trachealis to drugs.
Effects of inhibitors of arachidonic acid metabolism on Paf‐induced gastric mucosal necrosis and haemoconcentration
Authors: Wallace John L. , Whittle Brendan J.R. 
Published: July 2012

The effects of several inhibitors of arachidonic acid metabolism on gastric necrosis, hypotension, haemoconcentration, leukopenia and plasma exudation induced by platelet‐activating factor (Paf) were studied in the rat.
A 10 min intravenous infusion of Paf (100 ng kg−1 min−1) caused extensive gastric damage and a marked fall in systemic blood pressure which had not recovered to basal levels 30 min after the infusion had been terminated. Paf also caused significant haemoconcentration, plasma exudation and transient leukopenia.
Pretreatment with dexamethasone (0.2 or 2 mg kg−1 s.c.) or prednisolone (20 mg kg−1 s.c.) two hours before Paf significantly reduced the gastric damage and accelerated the recovery of blood pressure after the Paf infusion. Likewise, BW755C (50 mg kg−1 p.o.) significantly reduced the gastric damage.
Acute pretreatment with dexamethasone (2 mg kg−1 i.v.) 15 min before Paf, or with indomethacin (5 mg kg−1 s.c.), acetylsalicylic acid (10 mg kg−1 i.v.) or 1‐benzylimidazole (50 mg kg−1 s.c.) did not significantly affect the gastric damage induced by Paf.
The Paf‐induced haemoconcentration and plasma exudation were significantly reduced by pretreatment with prednisolone (20 mg kg−1 s.c.) or BW755C (50 mg kg−1 p.o.), while Paf‐induced leukopenia was unaffected by either drug.
These studies indicate that cyclo‐oxygenase products of arachidonic acid are unlikely to contribute significantly to the gastric damage or the prolonged hypotension induced by Paf. The ability of corticosteroids and BW755C to reduce the gastric damage, haemoconcentration and plasma exudation suggests that lipoxygenase products of arachidonic acid may contribute to these actions of Paf.
The binding of pirenzepine to digitonin‐solubilized muscarinic acetylcholine receptors from the rat myocardium
Authors: Birdsall N.J.M. , Hulme E.C. , Keen M. 
Published: July 2012

The binding of pirenzepine to digitonin‐solubilized rat myocardial muscarinic acetylcholine receptors has been examined at 4°C.
Solubilization produced only small changes in the binding of N‐methylscopolamine and atropine. In contrast to the low affinity binding of pirenzepine found to be present in the membranes, high affinity binding was detected in the soluble preparation. In both preparations, pirenzepine binding was complex.
High affinity pirenzepine binding (KD ∼ 3 × 10−8M) to the soluble myocardial receptors could be monitored directly using [3H]‐pirenzepine.
[3H]‐pirenzepine‐labelled soluble myocardial receptors have a sedimentation coefficient of 11.1 s. This indicates that [3H]‐pirenzepine binds predominantly to the uncoupled form of the receptor. However, [3H]‐ pirenzepine‐agonist competition experiments indicated that the high affinity pirenzepine binding sites are capable of coupling with a guanosine 5′‐triphosphate (GTP)‐binding protein. Pirenzepine affinities for the soluble myocardial receptors were unaffected by their state of association with the GTP‐binding proteins found in the heart.
The equilibrium binding properties of the soluble cortical and myocardial receptors were very similar. However, the binding kinetics of the myocardial receptor were much slower.
It appears that the membrane environment can affect the affinity of pirenzepine for the rat myocardial muscarinic receptor. Removal of the constraint by solubilization allows the expression of high affinity pirenzepine binding.
Identification of 6‐oxo‐prostaglandin E1 as a naturally occurring prostanoid generated by rat lung
Authors: Berry C.N. , Griffiths R.J. , Hoult J.R.S. , Moore P.K. , Taylor G.W. 
Published: July 2012

The spontaneous release of prostanoids from rat isolated perfused lungs was studied after acid/organic extraction of perfusates by bioassay, radioimmunoassay, thin layer and high performance liquid chromatographic methods and by gas chromatography‐negative ion mass spectroscopy (g.c.‐n.i.m.s.).
An acid/organic extractable anti‐aggregatory vasodilator prostaglandin which inhibited the twitch response of the field‐stimulated guinea‐pig vas deferens was released from the Krebs‐perfused rat lung in nanogram amounts similar to those of other detected prostanoids. Parallel biological assay suggested that this prostaglandin had very closely similar pharmacological activity to authentic 6‐oxo‐prostaglandin E1 (6‐oxo‐PGE1), a metabolite of prostacyclin (PGI2) generated by the action of the enzyme 9‐hydroxyprostaglandin dehydrogenase (9‐PGDH).
6‐oxo‐PGE1 was identified conclusively in extracts of rat lung perfusate by thin layer chromatography, high performance liquid chromatography and g.c./m.s. combined with bioassay (inhibition of platelet aggregation), and its covalent structure was defined by g.c. negative ion chemical ionization mass spectroscopy.
The rank order of spontaneous release of prostanoids (measured by radioimmunoassay) from the perfused rat lung was 6‐oxo‐PGF1α > thromboxane B2 (TXB2) > PGE2 > 6‐oxo‐PGE1 (measured biologically) > PGF2α. Release of all five prostanoids was inhibited by indomethacin, but only that of 6‐oxo‐PGE1 was inhibited by naringenin.
Rat lung 100,000 g cytosolic supernatants contained 9‐PGDH activity capable of removing 9β‐tritium from labelled prostacyclin and forming an acid/organic extractable 6‐oxo‐PGE1‐like anti‐aggregatory substance. This 9‐PGDH activity was inhibited by naringenin (IC50 10.3 μM).
The relevance of these findings to the possible physiological role of 6‐OXO‐PGE1 in the lung is discussed, and we propose that 6‐oxo‐PGE1 should be accorded the status of a physiologically relevant, naturally occurring metabolite of arachidonic acid.
The inhibitory action of 5‐hydroxytryptamine on gastric secretory function in rats
Authors: Cho C.H. , Ogle C.W. 
Published: July 2012

The inhibitory action of 5‐hydroxytryptamine (5‐HT) on gastric function was studied in vagotomized rats.
5‐HT (0.6, 1 or 5 mg kg−1, s.c.) dose‐dependently reduced gastric acid secretion evoked by histamine, pentagastrin or methacholine. Pepsin secretion induced by pentagastrin or methacholine was also depressed by 5‐HT.
Basal secretion of both acid and pepsin was not significantly affected by any of the three 5‐HT doses.
Indomethacin pretreatment, which significantly decreased gastric mucosal prostaglandin E2 content, did not modify the inhibitory effects of 5‐HT on histamine‐induced acid secretion, nor did phentolamine or propranolol.
This study suggests that 5‐HT inhibits gastric secretory function through mechanisms other than by sympathetic influence or increased prostaglandin synthesis. The inhibitory action appears not to be vagus‐dependent. Other mechanisms of action are discussed.