bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic capsaicin treatment impairs the micturition reflex in the rat
Authors: Holzer‐Petsche Ulrike , Lembeck Fred 
Published: July 2012

Filling the urinary bladder via a urethral cannula and preventing its voiding in anaesthetized rats led to rhythmic contractions of the detrusor muscle, which lasted for more than 1 h. This rhythmic activity ceased about 30 min after a s.c. injection of 50 mg kg−1 capsaicin. The contractile response of the detrusor to topically applied capsaicin was lost after systemic administration of the toxin, whereas no change in the sensitivity to acetylcholine was observed.
Urinary bladders of normal rats had a capacity of about 1 ml. Bladders of rats treated with capsaicin as neonates held a volume of more than 5 ml without contracting. Such bladders were insensitive to topically applied capsaicin but they contracted to acetylcholine as strongly as the bladders of control rats.
During an observation period of 3 days control rats gained weight at night and lost weight by day. Rats treated with capsaicin as neonates showed little fluctuation in body weight. Such rats hardly excreted any urine by day although at night they excreted as much as controls.
A water load of 5 ml 100 g−1 was excreted by control rats within 3 h. Rats treated with capsaicin as neonates excreted only half as much. In addition, 50% of the water load was excreted far later by capsaicin treated rats than by controls. Few changes were observed in rats treated with capsaicin as adults.
It is concluded that all primary afferent fibres mediating the sensation of a full bladder are capsaicin‐sensitive. An additional effect of capsaicin on renal mechanisms cannot be excluded.
Interactions of inhibitors of the lipoxygenase and cyclo‐oxygenase pathways with a supplementary binding site on soybean lipoxygenase
Authors: Baumann I. , Baumann J. , Wurm G. 
Published: July 2012

The oxygenation of [1‐14C]‐arachidonic acid by a soluble soybean lipoxygenase (E.C.1.13.11.12) preparation was determined in the presence of various cyclo‐oxygenase and lipoxygenase inhibitors. The results showed that several non‐inhibitory compounds drastically blunted the inhibitory potency of potent lipoxygenase inhibitors.
Studies on the combined effects of a variety of structurally unrelated inhibitors of lipoxygenase, cyclo‐oxygenase or both oxygenation pathways provided strong evidence for the existence of a supplementary binding site on soybean lipoxygenase which reduces the effective interactions of inhibitors with the catalytic site.
Thus several cyclo‐oxygenase inhibitors (which do not inhibit at the lipoxygenase catalytic site), as well as low concentrations of lipoxygenase inhibitors, interact with this putative supplementary site and blunt the inhibitory efficacy of potent lipoxygenase inhibitors.
Although the degree of interaction with the catalytic site determines the absolute potency of inhibitors, the additional interaction at the putative supplementary binding site is also obligatory for inhibitory potency.
In this new multiple‐site model the potent lipoxygenase inhibitors (e.g. acetone phenylhydrazone, phenidone) possess high affinities for both sites, whereas weak inhibitors and certain cyclo‐oxygenase inhibitors (e.g. benoxaprofen, phenylbutazone, indomethacin) interact predominantly with the supplementary site on the lipoxygenase but lack affinity for the catalytic site.
Effects on rabbit cardiac potentials of aprindine and indecainide, a new antiarrhythmic agent, in normoxia and hypoxia
Authors: Dennis P.D. , Williams E.M. Vaughan 
Published: July 2012

Intracellular potentials were recorded from rabbit atria, cardiac Purkinje cells and papillary muscles before and after exposure to various concentrations of indecainide. The effects of aprindine also were studied in the atrial preparations.
Both drugs depressed the maximum rate of depolarization (MRD) in a dose‐related manner, indecainide being approximately ten times more potent than aprindine.
Aprindine caused a dose‐related bradycardia, but indecainide had no significant effect on sinus node frequency.
Indecainide had a dose‐related negatively inotropic effect in normal, half‐normal and twice‐normal extracellular calcium concentrations.
Indecainide shortened action potential duration (APD) in atrium and Purkinje cells but prolonged APD to 50% repolarization in ventricular muscle.
The actions of indecainide were extremely persistent. No significant recovery of MRD was observed after pauses in stimulation of up to 16 s.
Indecainide had no effect on effective refractory period (ERP) measured by interpolated premature stimuli.
Indecainide is therefore categorized as a Class 1c antiarrhythmic agent.
The effects of both aprindine and indecainide on MRD were increased in hypoxic atria. Conduction velocity in hypoxic atria exposed to indecainide was greater than in controls, however, suggesting the possibility of improved cell‐to‐cell coupling.
A microiontophoretic study of the actions of the putative sleep factor, piperidine, in the rat brainstem
Authors: Horton R.C. , Logan S.D. , Wolstencroft J.H. 
Published: July 2012

By means of microiontophoresis, we have compared the actions of a putative sleep substance, piperidine, with other neurotransmitters in the rat anaesthetized with urethane.
In the pons and midbrain, piperidine mimicked the actions of acetykholine on more than 200 neurones. Piperidine‐ and acetylcholine‐induced excitations were equally effectively antagonized by hexamethonium or atropine.
In 32 neurones piperidine showed no affinity for the receptors for the excitatory amino acid agonists, quisqualate and N‐methyl‐D‐aspartate, piperidine‐evoked excitations being unaffected by the antagonists glutamate diethylester or 2‐amino‐5‐phosphonovalerate.
Similarly, piperidine‐evoked excitations in 23 neurones were unaffected by α‐methylnoradrenaline, suggesting that piperidine does not act at receptors for noradrenaline.
Twenty per cent of neurones responsive to piperidine were inhibited. These inhibitions in 12 neurones were insensitive to either strychnine or bicuculline indicating that piperidine does not act on receptors for glycine or γ‐aminobutyric acid.
In a further 68 neurones, neither hexamethonium (4 out of 59 cells) nor atropine (0 out of 9 cells) was effective in antagonizing the inhibitions evoked by piperidine or by acetylcholine.
It is suggested that piperidine may exert its central hypnogenic effects by an action at cholinoceptors in brainstem areas involved in sleep regulation.
Ventilatory stimulation by dopamine‐receptor antagonists in the mouse
Authors: Olson L.G. , Saunders N.A. 
Published: July 2012

Ventilation was measured by a plethysmographic method in awake mice before and after intraperitoneal injection of neuroleptic drugs to test the hypothesis that dopaminergic mechanisms modulate control of breathing in this species.
Dose‐dependent augmentation of ventilation at rest and during hypoxia, and reduced ventilation during hypercapnia was demonstrated for haloperidol, droperidol, prochlorperazine and chlorpromazine (P < 0.05 or less for each drug).
Doses of drugs causing maximal increase of the ventilatory response to hypoxia were linearly related (r = 0.98, P < 0.001) to in vitro affinity of the drugs for dopamine receptors.
Despite presumed equal dopamine‐receptor blockade, the drugs had unequal effects on the ventilatory response to hypoxia. Droperidol augmented hypoxic ventilation to 290% of the control value, chlorpromazine to 250% control, prochlorperazine to 190% control and haloperidol to 120% control. These differences in efficacy were in the same order as the affinities of the drugs for α‐adrenoceptors.
The effect of combined haloperidol (90 nmol kg−1) and varying doses of phentolamine (175–900 nmol kg−1) was assessed to test the hypothesis that α‐antagonism was a factor in determining the increase in ventilation following dopamine blockade. Phentolamine caused dose‐dependent augmentation of the ventilatory effects of haloperidol (P < 0.01) but had no ventilatory effect when given alone.
Carotid body resection in anaesthetized mice abolished the stimulation of hypoxic ventilation caused by droperidol.
It is concluded that dopaminergic mechanisms in the carotid body modulate ventilatory control in the awake mouse. The drugs most effective in augmenting hypoxic ventilation are those that block both dopamine and α‐adrenoceptors.
Effects of 3,4‐diaminopyridine and tetraethylammonium on the pre‐ and post‐junctional α‐adrenoceptor mediated inhibitory actions of noradrenaline in the guinea‐pig ileum
Authors: Bauer V. 
Published: July 2012

The effects of potassium channel blockers, 3,4‐diaminopyridine (DAP) and tetraethylammonium (TEA) were studied on the pre‐ and post‐junctional α2‐adrenoceptor mediated effects of noradrenaline in the guinea‐pig proximal ileum.
Both DAP (4 to 500 μmol 1−1) and TEA (0.3 to 3 mmol 1−1) transiently increased the basal tension of the ileum. However, DAP also increased the amplitude of the smooth muscle twitches evoked by transmural nerve stimulation, whereas TEA marginally depressed them.
Atropine (2 μmol 1−1) antagonized the contractions induced by DAP but did not affect the similar effects of TEA. On the other hand, DAP restored the smooth muscle twitches depressed by atropine, while TEA did not.
DAP, in a concentration‐dependent manner, reduced or abolished the prejunctional inhibitory α2‐adrenoceptor mediated effect of noradrenaline, whereas TEA (up to 3 mmol 1−1) was almost ineffective.
The postjunctional inhibitory α2‐adrenoceptor mediated effect of noradrenaline was attenuated even at the smallest TEA concentration used (0.3 mmol 1−1) and its postjunctional stimulatory α1‐adrenoceptor mediated effect was unmasked. However, DAP, was only marginally effective, even at the highest concentrations used (100 and 500 μmol 1−1).
From these results it would appear that in both the pre‐ and post‐junctional inhibitory α2‐adrenoceptor mediated actions of noradrenaline in the guinea‐pig ileum the primary step might be an increased potassium conductance. However, the potassium channels on the neuronal and the smooth muscle membrane have different sensitivities to DAP and TEA.
The potencies and selectivities of four calcium antagonists as inhibitors of uterine contractions in the rat in vivo
Authors: Abel Margaret H. , Hollingsworth M. 
Published: July 2012

The potencies of four calcium antagonists (nifedipine, gallopamil, verapamil and diltiazem) at inhibiting uterine contractions in vivo have been assessed in the conscious ovariectomized, post‐partum rat. Their selectivities for this action, relative to their effects on blood pressure and heart rate, have been compared with salbutamol.
All compounds produced a dose‐dependent inhibition of intra‐uterine pressure cycles. The rank order of potency was salbutamol >nifedipine > diltiazem = gallopamil > verapamil.
All compounds produced a dose‐dependent fall of mean blood pressure. The rank order of potency was salbutamol > nifedipine > gallopamil > verapamil > diltiazem.
Salbutamol and nifedipine produced a tachycardia, which was very marked with salbutamol. Gallopamil, verapamil and diltiazem induced a moderate tachycardia at low doses but temporary cessation of heart beat occurred at high doses.
Nifedipine and diltiazem, like salbutamol, exhibited some selectivity for inhibition of uterine contractions relative to their cardiovascular actions. Gallopamil and verapamil showed no selectivity for the uterus.
PACPX ‐ a substituted xanthine ‐ antagonizes both the A1 and A2 subclasses of the P1‐purinoceptor: antagonism of the A2 subclass is competitive but antagonism of the A1 subclass is not
Authors: Burnstock Geoffrey , Hoyle Charles H.V. 
Published: July 2012

1,3‐Dipropyl‐8‐(2‐amino‐4‐chlorophenyl)xanthine (PACPX) was examined for its ability to antagonize adenosine acting on the A1 and A2 subclasses of the P1‐purinoceptor. A1‐purinoceptors were studied in the isolated, driven left atria of the guinea‐pig, and A2‐purinoceptors in the isolated, carbachol‐contracted taenia coli of the guinea‐pig.
PACPX antagonized the actions of adenosine in both types of preparation and was a more potent antagonist than 8‐phenyltheophylline.
The antagonism at the A2‐purinoceptor was competitive with a pA2 of 5.95.
The antagonism at the A1‐purinoceptor was not competitive, although antagonism at the A1‐purinoceptor was greater than that at the A2‐purinoceptor, based on a comparison of pD2 values.
The manner of antagonism of PACPX on the A1‐purinoceptors of the heart was different from that found for the A1‐receptors in bovine brain, implying that there is a fundamental difference between these central and peripheral A1 subclasses of P1‐purinoceptor.
Pharmacological modulation of responses of guinea‐pig airways contracted with arachidonic acid
Authors: Burka John F. 
Published: July 2012

Arachidonic acid (AA) was used to induce contractions of guinea‐pig tracheal and lung parenchymal preparations in the presence of indomethacin.
Prior addition of FPL55712, nordihydroguaiaretic acid (NDGA), piriprost, benoxaprofen or nafazatrom, in order of potency, inhibited AA‐induced contractions of trachea. Higher concentrations (2–3 fold) were necessary to inhibit contractions of parenchyma.
FPL55712 and piriprost appeared to act as pharmacological antagonists of leukotrienes because they rapidly reduced the tone of the airways established by AA.
Administration of exogenous AA to indomethacin‐treated trachea appears to be a good model to examine leukotriene receptor antagonists and inhibitors of the lipoxygenase pathway.
Effects of raised intracranial pressure on regional cerebral blood flow: a comparison of effects of naloxone and TRH on the microcirculation in partial cerebral ischaemia
Authors: Koskinen Lars‐Owe D. 
Published: July 2012

The effects on regional cerebral blood flow (rCBF) of raised intracranial pressure (ICP) and of naloxone and thryrotropin releasing hormome (TRH) during this condition were studied in anaesthetized rabbits.
The ICP was elevated until a central ischaemic response was observed. The regional blood flow was determined with the microsphere technique before and during elevation of the ICP (ICPc) and after drug treatment.
Total CBF was reduced by about 70% during ICPc while the uveal blood flow increased slightly and some other peripheral tissue blood flows remained unaffected.
The administration of TRH caused an increase in mean arterial blood pressure (MAP) from 11.9 ± 0.6 to 14.6 ± 0.7 kPa and a normalization of the rCBF. In some peripheral tissues, e.g. gastric mucosa and spleen, TRH reduced the blood flow by 53% and 76%, respectively. In blood pressure stabilized animals no effect on rCBF was seen after TRH.
Naloxone had no consistent effect on MAP or local blood flow.
It was concluded that in the range of cerebral perfusion pressure studied there was a passive relationship between cerebral blood flow and perfusion pressure. The lack of effect of naloxone and the marked effect of TRH during cerebral ischaemia are consistent with a mechanism of action of TRH not related to a ‘physiological’ antagonism of opioids.
Two types of receptors for 5‐hydroxytryptamine on the cholinergic nerves of the guinea‐pig myenteric plexus
Authors: Kilbinger H. , Pfeuffer‐Friederich I. 
Published: July 2012

The effects of 5‐hydroxytryptamine (5‐HT) on spontaneous and electrically‐evoked release of [3H]‐acetylcholine (ACh) from guinea‐pig myenteric plexus preparations preincubated with [3H]‐choline have been investigated in the absence of cholinesterase inhibitors.
5‐HT caused a transient increase in spontaneous release and an inhibition of the electrically‐evoked release of [3H]‐ACh. The 5‐HT‐induced contractions of the longitudinal muscle were clearly related to the increase in spontaneous release. The inhibitory effect was not due to activation of α‐adrenoceptors since it was also observed in the presence of tolazoline and on strips from reserpine‐pretreated guinea‐pigs.
After desensitization of the excitatory 5‐HT receptors with 5‐HT or metoclopramide the effects of 5‐HT on spontaneous [3H]‐ACh release were largely reduced. A variety of established antagonists at neuronal 5‐HT receptors (i.e. metitepine 0.1‐1 μM; methysergide 1 μM; ketanserin 0.1‐1 μM; MDL 72222 0.1 μM; tropacocaine 1 μM) failed to block the excitation.
The inhibition by 5‐HT of the electrically evoked [3H]‐ACh release was competitively antagonized by metitepine (pA2 7.6) and methysergide (pA2 7.0) but not by ketanserin. Tachyphylaxis to the inhibitory action of 5‐HT did not occur.
The results suggest that the excitatory 5‐HT receptor (‘M’‐receptor) differs in its pharmacological properties from other neuronal 5‐HT receptors. The presynaptically located inhibitory receptor may roughly correspond to the 5‐HT, receptor subtype but probably differs from the 5‐HT autoreceptor.
Modification of blood pressure and nictitating membrane response to sympathetic amines by selective monoamine oxidase inhibitors, types A and B, in the cat
Authors: Finberg J.P.M. , Youdim Moussa B.H. 
Published: July 2012

The selective monoamine oxidase (MAO) inhibitors clorgyline, selegiline and AGN 1135 did not cause a change in responses of the cat nictitating membrane to preganglionic sympathetic nerve stimulation at 5 Hz.
Both selective MAO‐A and MAO‐B inhibitors markedly potentiated nictitating membrane contractions in response to β‐phenylethylamine (PEA). However, the responses to tyramine were unchanged.
The pressor responses to tyramine were potentiated by the selective MAO‐A inhibitor clorgyline (2 mg kg−1) but not by selegiline (1.0 mg kg−1) and AGN 1135 (1.5 mg kg−1), selective MAO‐B inhibitors.
At the doses used selegiline and AGN 1135 caused a near total selective inhibition of liver and brain MAO‐B, while clorgyline inhibited MAO‐A only in the brain.
AGN 1135, like selegiline, could be a useful drug in potentiating the action of L‐DOPA in Parkinson's disease.
Cardioprotection by the calcium antagonist PN 200‐110 in the absence and presence of cardiodepression
Authors: Cook N.S. , Hof R.P. 
Published: July 2012

The globally‐ischaemic Langendorff rabbit heart model has been used to study the cardioprotective effects of the dihydropyridine PN 200‐110 (PN) at two doses, one having no negative inotropic effect and a higher dose causing a 62 ± 5% reduction in contractility.
Following 45 min no‐flow global ischaemia, recovery was monitored for a period of 90 min reperfusion. Hearts were paced at a constant rate throughout experiments. Contractile force and coronary flow were recorded continuously. Tracer microspheres were injected at regular intervals to assess regional flow distributions, drill biopsies were taken to determine tissue high energy phosphate content, and enzyme leakage in the coronary effluent measured during the first 15 min of reperfusion.
Untreated hearts recovered 21 ±2% of their initial contractile force and flow to all heart regions was reduced. In particular, endocardial flow fell to 20% of its pre‐ischaemic level, with the ratio of flow to the endocardium (endo)/epicardium (epi) decreasing from ca. 1.0 to 0.4.
Hearts treated with 2 × 10−8 M PN (included in the perfusate from 30 min before ischaemia until 30 min after ischaemia) recovered 49 ± 2% of their initial, pretreatment contractile force, and following the ischaemia the endo/epi ratio was not significantly changed from the pre‐ischaemic value.
The lower PN dose (3 × 10−10 M) afforded a lesser degree of protection, contractility recovering to 29 ± 4% of the initial level, with an endo/epi ratio of 0.7 after 90 min reperfusion.
The two PN doses afforded a similar degree of protection against enzyme leakage which was in both cases significantly less than in untreated hearts.
Myocardial ATP and creatine phosphate content was markedly reduced by the ischaemic episode. Neither PN dose modified this depletion.
These results suggest that whilst cardiodepression may well offer protection against ischaemic damage, this is not the sole mechanism wherby PN (and possibly other calcium antagonists) can protect the heart. Preservation of blood flow to the inner layers of the left ventricular wall is likely to be one of the major factors underlying the enhanced recovery shown by PN.
Actions of ATP and α,β‐methylene ATP on neuromuscular transmission and smooth muscle membrane of the rabbit and guinea‐pig mesenteric arteries
Authors: Ishikawa Shiro 
Published: July 2012

In the rabbit mesenteric artery, adenosine triphosphate (ATP), showed two actions on the membrane potential of muscle cells: low concentrations (1–10 μM) hyperpolarized and high concentrations (> 50 μM) depolarized the membrane. Both changes in the potential were accompanied by increases in ionic conductance.
In the rabbit mesenteric artery, α,β‐methylene ATP (MeATP), (> 30 nM) depolarized the muscle membrane at a lower concentration than ATP (> 50 μM), and increased the ionic conductance of the membrane. The depolarization induced by ATP was prevented by low concentrations of MeATP, but the hyperpolarization was retained. Furthermore, the hyperpolarization was not affected by theophylline (10 μM).
In the guinea‐pig mesenteric artery, ATP and MeATP depolarized and increased the ionic conductance of muscle membrane, but to depolarize the membrane, higher concentrations of both agents were required, compared to those in the rabbit mesenteric artery.
In the mesenteric arteries from both species, perivascular nerve stimulation evoked excitatory junction potentials (e.j.ps). In both tissues, MeATP inhibited the amplitude of e.j.ps at lower concentrations than did ATP, and both agents had more potent inhibitory actions on rabbit than on guinea‐pig. The inhibition of e.j.p. induced by low concentrations of these agents showed no relationship to depolarization, but the inhibition induced by high concentrations was paralleled by depolarization and increase in ionic conductance of the membrane.
In the rabbit mesenteric artery, overflow of noradrenaline (NA) and its metabolite (3,4‐dihydroxyphenylglycol; DOPEG) produced by perivascular nerve stimulation was examined. ATP (0.1 mM) but not MeATP (0.1 μM) reduced the overflow of NA, whereas both agents had no effect on the overflow of DOPEG.
Exogenously applied high concentrations of NA (> 3 μM) depolarized the muscle membrane in both species. These NA‐induced depolarizations were not affected by treatment with ATP or MeATP.
It is concluded that, in the rabbit mesenteric artery, ATP is more likely to be involved in generation of e.j.ps than is NA. A similar interpretation in the guinea‐pig mesenteric artery is complicated by the depolarization produced by high concentrations of ATP or MeATP.