bluuebunny/crossref_metadata_2025_split huggingface dataset:
Captopril potentiates the vasodepressor action of Met‐enkephalin in the anaesthetized rat
Authors: Di Nicolantonio R. , Hutchinson J.S. , Takata Y. , Veroni M. 
Published: July 2012

The transient vasodepressor action of Met‐enkephalin (10–80 μg kg−1, i.v.) in anaesthetized rats was significantly potentiated by the angiotensin‐converting enzyme inhibitor, captopril (2 mg kg−1, i.v.); at this dose, it failed to modify the transient vasodepressor action of the non‐specific vasodilator, nitroprusside (2.5, 5.0, 10 μg kg−1, i.v.).
Captopril (2 mg kg−1, i.v.) caused a slow, progressive fall in the blood pressure of anaesthetized spontaneously hypertensive (SH) rats when compared to vehicle‐treated controls. Pretreatment with naloxone (1.5 mg kg−1, i.v.) 30 min earlier failed to alter significantly the hypotensive action of captopril in anaesthetized SH rats.
It was concluded that although captopril potentiated the vasodepressor action of Met‐enkephalin in anaesthetized normotensive rats, potentiation of endogenous opioids does not appear to be involved in the hypotensive action of captopril in anaesthetized SH rats.
Effects of amrinone on the transmembrane action potential of rabbit sinus node pacemaker cells
Authors: Kodama Itsuo , Kondo Noriaki , Shibata Shoji 
Published: July 2012

Effects of amrinone on the membrane action potential and spontaneous activity were investigated in sinus node pacemaker cells of rabbit heart by use of microelectrode techniques.
Amrinone (1 × 10−4m to 6 × 106m) caused a shortening of cycle length of spontaneous firing (SPCL) accompanied by an increase in the maximum upstroke velocity at phase 0 () and amplitude of action potential (AAP), while it did not affect the maximum diastolic potential (MDP).
All the effects of amrinone on sinus node pacemaker cells were markedly attenuated or abolished in a low calcium medium (Ca+0.1 mm or 0.3 mm) or in the presence of the slow channel blocking agent, verapamil (5 × 10−7m, 2 × 106m).
The effects of amrinone were not antagonized by the β‐adrenoceptor blocking agent, pindolol (2 × 10−7m).
These results indicate that amrinone has an intrinsic effect on sinus node pacemaker cells, increasing their spontaneous firing activity.
It is also assumed that the effects of amrinone on sinus node cells are probably mediated by an augmentation of the slow calcium and/or sodium inward current through the cell membrane.
The potentiation of taurocholate‐induced rat gastric erosions following parenteral administration of cyclo‐oxygenase inhibitors
Authors: Whittle B.J.R. 
Published: July 2012

Subcutaneous administration of anti‐inflammatory doses of aspirin, indomethacin, naproxen and flurbiprofen inhibited prostacyclin formation ex vivo in the luminally‐perfused gastric mucosa of anaesthetized rats.
These doses of anti‐inflammatory compounds potentiated the formation of gastric mucosal erosions following 3 h luminal perfusion of the topical irritant, acidified sodium taurocholate (2 mm in 100 mm HCl).
The increase in luminal acid‐loss during gastric perfusion of acidified taurocholate was not significantly enhanced by these anti‐inflammatory agents.
A correlation was found between the increase in gastric erosion formation and the inhibition of mucosal prostacyclin formation ex vivo by intravenous injection of aspirin or ketoprofen during acid‐taurocholate perfusion.
BW755C, which failed to inhibit mucosal prostacyclin formation ex vivo, did not significantly augment acid‐taurocholate induced gastric damage.
The present findings support the potentiating interactions between topical irritation and inhibition of gastric cyclo‐oxygenase in the genesis of the gastric lesions.
Nicotinamide adenine dinucleotide depresses synaptic transmission in the hippocampus and has specific binding sites on the synaptic membranes
Authors: Richards C.D. , Snell C.R. , Snell P.H. 
Published: July 2012

The electrical activity of transverse slices of hippocampus was used as a bioassay in which extracts of fresh brain tissue were screened for biological activity. A factor that depressed synaptic transmission was identified as nicotinamide adenine dinucleotide (NAD). This depressant action of NAD could be observed at concentrations in the range 1–10μm and the degree of depression was monotonically related to the concentration of NAD in the bathing medium.
NAD did not affect the antidromic invasion of the granule cells nor did it alter the relationship between the electrically evoked excitatory postsynaptic field potential (e.p.s.p.) and the population discharge of the granule cells (population spike). These results suggest that NAD did not affect the electrical excitability of the neuronal membranes.
NAD had little effect on the sensitivity of granule cells to iontophoretically applied L‐glutamate, the putative excitatory transmitter for the perforant path‐granule cell pathway.
Pure synaptosomal membranes, free of mitochondria, had two binding sites for NAD: a high affinity site with a Kd of 1 μm and a low affinity site with a Kd of 17 μm. These sites were similar in affinity to those of mitochondria, although the density of the high affinity sites was 5 × greater in the synaptosomal membranes. Adenosine had a relatively weak affinity for the NAD binding sites.
It was concluded that NAD probably depressed synaptic transmission in the dentate gyrus by binding to sites on the presynaptic nerve terminal and reducing the amount of transmitter released by a nerve impulse. The physiological significance of this view is discussed.
Biphasic non‐adrenergic, non‐cholinergic relaxations of the mouse anococcygeus muscle
Authors: Gibson A. , Yu O. 
Published: July 2012

Trains of field stimulation of 60 s duration caused a biphasic relaxation of carbachol (50 μm)‐induced tone in the mouse anococcygeus. The optimal pulse frequency and width were 10 Hz and 1 ms respectively.
Tetrodotoxin (31, 124, and 310 nm) caused a dose‐dependent reduction in the magnitude of both phases. Neither phase was affected by (±)‐propranolol (1 μm), neostigmine (1 μm), (+)‐tubocurarine (100 μm), or apamin (500 nm). Biphasic relaxations were observed in muscles from 6‐hydroxydopamine pretreated mice.
Haemolysed blood (10, 40, and 100 μm) reduced the magnitude of the first phase of nerve‐induced relaxation to a greater extent than the second. This effect was reversible.
Following a prolonged train of inhibitory nerve stimulation (10 Hz; 10 min) the magnitude of the first phase was reduced only slightly, but the second markedly.
The possible relationships between the biphasic relaxation to field stimulation and putative non‐adrenergic, non‐cholinergic transmitters in the mouse anococcygeus are discussed.
Morphine‐neural interactions on canine intestinal absorption and blood flow
Authors: Mailman David 
Published: July 2012

Intestinal Na and H2O fluxes and blood flow were determined in extrinsically denervated or innervated ileum of fed dogs during intra‐arterial (0.2, 2, 20 μg min−1) or intraluminal (4, 40, 400 μg ml−1) morphine sulphate infusion.
3H2O and 22Na were used to determine unidirectional fluxes and 3H2O clearances were used to determine total segmental and absorptive site blood flow.
Net Na and H2O absorption decreased with time in innervated gut segments but were unchanged in denervated segments.
Intra‐arterial morphine prevented the decrease in net Na and H2O absorption in innervated segments due to increases in unidirectional absorptive fluxes. Intra‐arterial morphine did not affect absorption in denervated segments.
Intraluminal morphine increased net Na and H2O absorption from both innervated and denervated ileal segments due to increases in the unidirectional absorptive fluxes.
Absorptive site blood flow was linearly related to unidirectional absorptive Na fluxes in each group although not with the same slopes. The increment in absorptive site blood flow vs. absorptive Na flux was greatest with luminal morphine, intermediate with intra‐arterial morphine and in denervated segments without morphine and least in innervated segments.
It was concluded that intra‐arterial morphine inhibits an antiabsorptive effect of extrinsic nerves and that intraluminal morphine promotes an absorptive effect which could be direct or mediated through intrinsic nerves.
Characterization of the α‐adrenoceptors in the female rabbit urethra
Authors: Andersson Karl‐Erik , Larsson Bengt , Sjögren Christer 
Published: July 2012

A radioligand binding technique was used to evaluate the proportions of α1‐ and α2‐adrenoceptors in crude membrane preparations obtained from the female rabbit bladder base and urethra. In addition, urethral rings were studied in vitro in an attempt to determine if α1‐ and/or α2‐adrenoceptors are located postjunctionally in the urethral smooth muscle.
Studies of the inhibition of [3H]‐dihydroergocryptine binding by the selective α1‐adrenoceptor antagonist prazosin or the selective α2‐adrenoceptor antagonist rauwolscine revealed the α‐adrenoceptor population to consist of approximately 25% α1‐adrenoceptors and 75% α2‐adrenoceptors. These proportions were confirmed in saturation studies with [3H]‐prazosin and [3H]‐rauwolscine. The sum of α1‐ and α2‐adrenoceptors labelled by these selective α1‐ and α2‐adrenoceptor antagonists was about equal to the number labelled by the non‐selective α‐adrenoceptor antagonist [3H]‐dihydroergocryptine.
Noradrenaline, as well as the selective α1‐adrenoceptor agonist phenylephrine and the selective α2‐adrenoceptor agonist clonidine, induced contractions of urethral ring preparations. Prazosin blocked contractions induced by phenylephrine to a greater extent than contractions induced by clonidine. The opposite was true for the inhibitory effect of rauwolscine.
In addition to showing that both α1‐ and α2‐adrenoceptor binding sites exist in membrane preparations of the rabbit bladder base and urethra, the results reveal the presence of both adrenoceptor subtypes postjunctionally in the rabbit urethra; and both mediate contraction of the smooth muscle.
The action of dantrolene sodium on individual fast and slow motor units of the rat anaesthetized with urethane
Authors: Leslie G.C. , Part N.J. 
Published: July 2012

Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a vehicle of 5% mannitol taken to pH 10 with NaOH.
The muscle relaxant action of dantrolene sodium was measured from the contractions of individual motor units of the extensor digitorum longus (EDL), soleus (SOL) and segmental tail (ST) muscles. Data were also collected from their parent whole muscle preparations.
The depressant action of dantrolene sodium on the percentage‐normalized amplitude of contraction of the individual motor units was greater than its effect on the whole muscle twitch amplitude, in all three muscles.
The twitch amplitude of fast contracting motor units was significantly more reduced (P < 0.001) by dantrolene sodium than was that of slow contracting motor units.
Dantrolene sodium reduced the contraction time of all motor units. The effect of the drug on half‐relaxation time varied within and between groups of motor units studied.
The drug was confirmed to have a greater depressant action on the twitch contraction than on the fused tetanus of whole muscle. This was true also for single motor units.
With tetanic stimulation the effect of dantrolene sodium was also dependent upon the motor unit type, fast or slow. A maximum depression of contractile tension occurred at a stimulation frequency of 64 Hz for fast EDL motor units whereas the maximum depression for ST slow units, the slowest units tested, was at a stimulation frequency of 14 Hz.
Release of endogenous 5‐hydroxytryptamine from the myenteric plexus of the guinea‐pig isolated small intestine
Authors: Holzer P. , Skofitsch G. 
Published: July 2012

The presence of 5‐hydroxytryptamine (5‐HT) and its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) in, and the release of these substances from, the myenteric plexus‐longitudinal muscle (MPLM) layer of the guinea‐pig isolated small intestine were investigated. 5‐HT and 5‐HIAA were measured by high performance liquid chromatography and electrochemical detection.
Freshly prepared MPLM contained measurable amounts of 5‐HT and 5‐HIAA. For the release experiments, the MPLM was incubated in a medium containing the 5‐HT uptake inhibitor fluoxetine and the monoamine oxidase inhibitor nialamide; this led to a decrease in the 5‐HIAA content of the MPLM whereas the 5‐HT content remained unchanged.
There was a spontaneous release of 5‐HT and 5‐HIAA from the MPLM. The release of 5‐HT was so small that it was just detectable; it seemed equivalent to about 0.8% of the tissue stores released per min.
Depolarization of the tissue by increasing the [K+] or by exposing it to veratridine enhanced the release of 5‐HT in a Ca2+‐dependent manner whereas the release of 5‐HIAA was not increased. Tetrodotoxin inhibited the veratridine‐evoked release of 5‐HT but did not affect the K+‐evoked release of 5‐HT.
The presence of 5‐HT in myenteric neurones and the characteristics of the release of 5‐HT from these neurones strongly support the hypothesis that 5‐HT is an enteric neurotransmitter.
Adrenergic transmission in the dog mesenteric vein and its modulation by α‐adrenoceptor antagonists
Authors: Suzuki H. 
Published: July 2012

Adrenergic transmission was investigated in the dog mesenteric vein by recording electrical responses of single smooth muscle cells to perivascular nerve stimulation.
Perivascular nerve stimulation generated an excitatory junction potential (e.j.p.) and a slow depolarization of the membrane. The amplitude of the e.j.p. was increased by increasing the stimulus intensity, and at high intensity, a spike potential was generated.
Repetitive stimulation of the nerves showed facilitation of e.j.ps and enhanced the amplitude of slow depolarization. A linear relationship was observed between the amplitude of the e.j.p. and of slow depolarization.
The slow depolarization was inhibited by application of yohimbine or phentolamine, but not by prazosin. The amplitude of e.j.p. was increased by prazosin and was decreased by yohimbine. Both e.j.p. and slow depolarization were inhibited by guanethidine or tetrodotoxin.
Exogenously applied noradrenaline depolarized the muscle membrane and, in high concentrations (> 10−7 m), generated slow waves. These effects of noradrenaline were blocked by yohimbine. High concentrations of prazosin (> 10−6m) showed weak inhibitory effects on the noradrenaline actions.
The amplitude of e.j.p. was decreased by exogenously applied noradrenaline in a dose‐dependent manner. The inhibitory effect of noradrenaline on the e.j.p. was suppressed by yohimbine, but not by prazosin or phentolamine.
Phentolamine, but not prazosin, enhanced the facilitation process of e.j.ps. This effect was not suppressed by exogenously applied noradrenaline.
Application of neostigmine but not of atropine, reduced the e.j.p. amplitude without affecting the slow depolarization.
It was concluded that, in the dog mesenteric vein, perivascular nerve stimulation produced three types of electrical responses of the smooth muscle membrane, i.e., e.j.p., slow depolarization and spike potential. The slow depolarization was generated by activation of α2‐adrenoceptors. Exogenously applied noradrenaline reduced the e.j.p. amplitude through activation of prejunctional α2‐adrenoceptors, but the reduction may not involve α‐autoinhibitory mechanisms.
The interaction between hexamethonium and tubocurarine on the rat neuromuscular junction
Authors: Rang H.P. , Rylett R. Jane 
Published: July 2012

The ability of hexamethonium (C6) to reverse the neuromuscular blocking action of tubocurarine (Tc) has been reinvestigated at the voltage clamped endplate of the omohyoid muscle of rat. The possibility that a weak anticholinesterase action of C6 could contribute to the paradoxical potentiation of the peak amplitude of the endplate response has been examined.
C6 (50–200 μm) caused an increase in the amplitude of nerve‐evoked endplate currents (e.p.cs) recorded in the presence of 0.6 μm Tc. The effect decreased with hyperpolarization of the muscle fibre. Irreversible inhibition of acetylcholinesterase resulted in a loss of the anti‐curare effect of C6.
C6 did not cause an increase in e.p.c. amplitude when acetylcholine (ACh) receptors were blocked irreversibly by α‐bungaratoxin. When transmission was blocked by increased Mg2+ concentration, C6 (50–400 μm) reduced the amplitude of e.p.cs without appreciably affecting their time course.
C6 caused a decrease in the amplitude of miniature endplate currents (m.e.p.cs) the effect being slightly increased when the fibre was hyperpolarized. An e‐fold increase in the effectiveness of C6 occurred with approximately 58 mV hyperpolarization. High concentrations (> 400 μm) affected the time course of m.e.p.cs in a manner suggestive of open channel block, but this was not evident at 200 μm, the concentration that was most effective in reversing Tc block.
When tested against responses to short ionophoretic pulses of agonists, C6 was less effective against ACh ((EC50 ca. 300 μm) than against carbachol (CCh) (EC50 100 μm). When cholinesterase was irreversibly inhibited, C6 blocked responses to both agonists equally (EC50 ca. 100 μm).
The effectiveness of C6 in blocking the action of CCh was reduced 10 fold in the presence of 0.6 μm Tc, implying that the two antagonists compete for the same binding site.
C6 (50–200 μm) in the presence of Tc (0.6 μm) increased the response to ionophoretically applied ACh but not that to CCh.
C6 was equipotent in blocking m.e.p.cs and responses to ionophoretically applied ACh whereas Tc was more potent against the exogenously applied agonist.
C6 was a weak inhibitor of acetylcholinesterase activity in rat muscle homogenates (EC50 1.5 mm).
The results are discussed in terms of the kinetic hypothesis advanced by Ginsborg & Stephenson (1974) to account for the Tc reversal phenomenon. It is concluded that this theory can explain most of the effect on e.p.cs, but that the weak anticholinesterase action of C6 is also a factor, particularly in the reversal of Tc block of ionophoretic responses.
Tolbutamide as a model drug for the study of enzyme induction and enzyme inhibition in the rat
Authors: Back D.J. , Sutcliffe F. , Tjia J.F. 
Published: July 2012

The effects of various drugs on the pharmacokinetics of tolbutamide have been examined in the rat.
Phenobarbitone pretreatment caused a significant decrease in half life and area under the curve (AUC) and a significant increase in clearance and volume of distribution (Vd).
Acute administration of primaquine significantly increased half life and AUC and decreased clearance. In contrast, the related animoquinolone chloroquine, was without effect.
Acute administration of cimetidine produced similar changes to primaquine but of lesser magnitude.
Formation of the major metabolite hydroxytolbutamide, was markedly enhanced by phenobarbitone and reduced by primaquine and cimetidine.
We conclude that due to its single pathway of metabolism, tolbutamide is a good substrate to use when examining pharmacokinetic interactions involving hepatic enzyme induction and inhibition.
The effect of acetylsalicylic acid on renal function in the Pekin duck
Authors: Gray D. A. , Langrieger N. , Reschmaier J. , Simon E. 
Published: July 2012

The acute effects of intravenously administered lysine‐acetylsalicylic acid (ASA) on renal function in the Pekin duck have been studied with special reference to possible interactions with the antidiuretic hormone, arginine vasotocin (AVT), in the control of renal water and solute output.
ASA produces an immediate increase in urine flow rate which is dose‐related in the range 25 to 100 mg kg−1 and is associated with a slight reduction in urine osmolality, but an overall increase in renal osmolal excretion affecting Na+, CI− and K+ to approximately equal extents.
The effects, which are similar in both saltwater and freshwater adapted ducks infused with hyposmotic saline or glucose solution, can also be produced by similar doses of sodium salicylate (SA).
The mechanism of action is probably not related to inhibition of prostaglandin synthetases.
There is no change in the glomerular filtration rate or peripheral blood pressure following the ASA injection.
There is no change in the circulating level of AVT; however, preliminary studies do not exclude the possibility of a partial antagonism of salicylate to AVT at the renal level.
Effects of phosphorothioate analogues of ATP, ADP and AMP on guinea‐pig taenia coli and urinary bladder
Authors: Burnstock G. , Cusack N.J. , Meldrum L. A. 
Published: July 2012

Phosphorothioate analogues of ATP, ADP and AMP were tested on the guinea‐pig taenia coli and urinary bladder.
The Rp diastereoisomers of the phosphorothioate analogues, ATP‐α‐S and ADP‐α‐S were respectively 7 and 3 times more effective than the Sp diastereoisomers in causing relaxation of the taenia coli. No stereoselectivity was observed for the diastereoisomers of ATP‐β‐S.
In guinea‐pig bladder, no stereoselectivity was observed for any of the phosphorothioate analogues.
These results show that P2‐purinoceptors mediating inhibitory responses in the guinea‐pig taenia coli show marked stereoselectivity, while P2‐purinoceptors mediating excitatory responses in the guinea‐pig bladder show little stereoselectivity.
Alteration of monocrotaline pyrrole‐induced cardiopulmonary effects in rats by hydralazine, dexamethasone or sulphinpyrazone
Authors: Hilliker Katherine S. , Roth Robert A. 
Published: July 2012

The effects of intraperitoneal hydralazine, dexamethasone, or sulphinpyrazone on the toxicity of monocrotaline pyrrole (MCTP) were examined in rats 14 days after injection of MCTP (5 mg kg−1, i.v.).
MCTP alone caused increases in lung weight, and of both lactate dehydrogenase activity and protein concentration in bronchopulmonary lavage fluid. Right ventricular hypertrophy also occurred.
Hydralazine (3 mg kg−1, daily), a vasodilator and platelet prostaglandin synthesis inhibitor, reduced the degree of right ventricular hypertrophy and the elevation in the concentration of protein in lavage fluid.
Dexamethasone (27 μg kg−1, daily), an anti‐inflammatory agent and inhibitor of phospholipase, also reduced the right ventricular hypertrophy and the increased protein concentration in lavage fluid caused by MCTP.
Sulphinpyrazone (100 mg kg−1, twice daily), an inhibitor of platelet prostaglandin biosynthesis, prevented right ventricular hypertrophy in the MCTP treated rats without affecting any of the indices of lung injury.
These results provide further support for the hypothesis that platelets and vasoconstrictor agents play a role in the development of MCTP‐induced pulmonary hypertension.