bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pardaxin produces postjunctional muscle contraction in guinea‐pig intestinal smooth muscle
Authors: Primor Naftali 
Published: July 2012

The action of pardaxin (PX), a toxin isolated from the secretion of the Red Sea flatfish, Pardachirus marmoratus, was studied on longitudinal muscle of guinea‐pig ileum.
Pardaxin contracted the ileum and subsequently abolished muscle contraction to 5‐hydroxytryptamine (5‐HT), but did not affect the responses to acetylcholine (ACh) and substance P(SP).
Pardaxin‐induced contraction was only partially suppressed by atropine and not affected by tetrodotoxin or morphine. Preparations desensitized to 5‐HT or SP responded normally to pardaxin.
Pardaxin‐induced contractions were normal in K+‐depolarizing Krebs Ringer solution and not affected by black widow spider venom.
It is concluded that the pardaxin‐induced muscle contractions are not mediated through the release of neurotransmitters and do not involve 5‐HT, SP or ACh receptors, but are due to a direct action on the muscle contractile mechanism.
The calcium antagonists PY 108–068 and verapamil diminish the effects of angiotensin II: sites of interaction in the peripheral circulation of anaesthetized cats
Authors: Hof R. P. 
Published: July 2012

The sites of interaction between the vasoconstrictor angiotensin II (A II) and the calcium antagonists PY 108–068 (PY) (a dihydropyridine derivative) or verapamil (V) in different peripheral vascular beds were investigated using the microsphere method in chloralose‐urethane anaesthetized open‐chested cats.
A II was infused intravenously into 27 cats at a rate of 0.15 μg kg−1 min−1. Systemic haemodynamic variables and regional blood flow were measured immediately before and 10 min after the start of the infusion.
While the infusion of A II continued, PY (3 μg kg−1 min−1), V (30 μg kg−1 min−1) or the vehicle was infused for 10 min into 9 cats each and the effects of this combined infusion were again measured at the end of the 10 min period.
A II increased mean arterial blood pressure but decreased peripheral conductance and, to a smaller but still significant degree, cardiac output and peak acceleration of blood in the aorta (an ejection phase parameter of myocardial contractility).
The calcium antagonists reversed these effects. Cardiac output and total peripheral conductance were increased even beyond the pre‐A II level by PY.
A II constricted the vascular beds of the kidney, small intestine, liver and skin. Arterio‐venous shunt flow decreased. Vasoconstriction was also found in the stomach, spleen and in different parts of the heart with the exception of the subendocardial layer of the left ventricle, where blood flow increased and conductance remained unchanged. A II did not decrease conductance in different parts of the brain or in skeletal muscle.
The vasoconstrictor effects of A II persisted or tended to be increased in most of the vascular beds of placebo treated animals. PY 108–068 and verapamil abolished the vasoconstrictor effects of A II in most of the vascular beds with the exception of the liver, the spleen, the skin and the arterio‐venous shunts and caused vasodilatation in the heart. PY also induced vasodilatation in the brain and skeletal muscle, where A II had not induced vasoconstriction.
The pattern of attenuation of A II effects was different from the pattern of vasodilatation induced by these and other calcium antagonists in the same cat preparation not treated with a vasoconstrictor. The sites of action of this dihydropyridine derivative (PY) on the peripheral circulation thus, appear to depend not only on the vascular bed but also on the presence of a vasoconstrictor influence at the time of investigation.
The time course of muscarinic depolarization of guinea‐pig myenteric neurones
Authors: North R. A. , Tokimasa T. 
Published: July 2012

Intracellular recordings were made from neurones in the myenteric plexus of the guinea‐pig ileum in vitro. Muscarinic depolarizations were evoked by brief (1–500 ms) ionophoretic applications of acetylcholine (ACh) or other agonists. Nicotinic responses to ACh evoked by the same ionophoretic pulse had short latencies and rapid rise times, indicating close proximity of the ionophoretic pipette to the neurone membrane.
The time course (duration several seconds) of the muscarinic depolarization was independent of the identity of the agonists applied (ACh, methacholine, carbachol, oxotremorine).
Hyoscine and barium were ejected onto the neurones by brief (30 ms‐1 s) pressure pulses applied to micropipettes. Hyoscine applied immediately after ACh, during the latency and rising phase of the muscarinic depolarization, did not antagonize the response to ACh. The same application of hyoscine immediately prior to ACh caused complete antagonism.
Muscarinic depolarizations evoked by continuous application of ACh (by repeated ionophoresis or perfusion) were reversed by hyoscine. The time course of this reversal was similar to the decline of the muscarinic response following a single brief application of ACh.
Barium caused a depolarization similar to that produced by muscarinic agonists in its latency, time course and temperature sensitivity, and having the same reversal potential (‐90 mV). These barium potentials were not affected by hyoscine.
It is suggested that neither diffusion of ACh to the receptors nor the kinetics of the agonist‐receptor interaction contributes significantly to the latency and prolonged time course of the muscarinic depolarization.
Action of ouabain on rat heart: comparison with its effect on guinea‐pig heart
Authors: Herzig Stefan , Mohr Klaus 
Published: July 2012

The inotropic dose‐response curve of ouabain in rat cardiac ventricular strips exceeded a concentration range of two decades (1 × 10−7 M to 3 × 10−5 M) displaying an intermediate plateau phase. In guinea‐pig ventricular strips the inotropic ouabain concentrations spanned only one decade (1 × 10−7 M‐1 × 10−6 M).
Ouabain‐intoxication in guinea‐pig ventricular strips occurring at 3 × 10−6 M consisted of arrhythmia and contracture, while in rat ventricular strips at the toxic concentration of 1 × 10−4 M only a progressive increase in diastolic tension was observed.
By means of atomic absorption spectroscopy the ouabain‐induced loss of cellular potassium and gain of sodium in rat ventricular strips was detected only at concentrations of ouabain higher than 10−4 M.
Ouabain reduced the activity of Na/K‐ATPase prepared from rat and guinea‐pig cardiac ventricles to half of its maximum at 6.5 × 10−5 M in rat and 1.0 × 10−6 M in guinea‐pig, rat heart Na/K‐ATPase thus being about 60 fold less sensitive towards ouabain.
Specific [3H]‐ouabain binding to membrane suspensions prepared from rat and guinea‐pig ventricles was characterized by a similar affinity in rat (KD = 4 × 10−8 M) and guinea‐pig (KD = 13 × 10−8 M). The number of ouabain binding sites in rat membranes was only about 10% of the number found in guinea‐pig membranes. In rat the presence of additional ouabain‐binding with low affinity and high capacity seemed possible, but could not be verified for methodological reasons.
In the light of the biochemical results and binding data, the wider range of ouabain concentration exerting a positive inotropic effect in the rat may be attributed to the existence in the latter of two populations of receptors with different affinities for ouabain and different capacities. In contrast, in the guinea‐pig, there is a single population. Nevertheless it is probable that all the receptors in both species are part of the Na/K‐ATPase complex and mediate a positive inotropic effect after ouabain‐binding in an identical manner.
Effect of bumetanide, frusemide and prostaglandin E2 on the isolated perfused kidney of rat and rabbit
Authors: Foy J.M. , Nuhu S.Z. 
Published: July 2012

Rat and rabbit kidneys were isolated, perfused via the renal artery with Krebs solution and perfusion pressure monitored. Dose‐response curves to noradrenaline administered as bolus doses or frequency‐response curves from transmural arterial electrical stimulation were obtained.
A 1 h continuous infusion of bumetanide (0.1 μg ml−1) increased the sensitivity of rat kidney vessels to noradrenaline, an effect also seen when bumetanide and flurbiprofen (6 μg ml−1) were simultaneously perfused. In the rabbit there was a decreased sensitivity to both electrical stimulation and noradrenaline.
A 1 h continuous infusion of frusemide (6 μg ml−1) only altered the effects of electrical stimulation. An increased sensitivity in the rat (abolished by flurbiprofen) and a decreased sensitivity in the rabbit kidney was observed.
A 1 h continuous infusion of prostaglandin (PG)E2 (2 ng ml−1) increased the sensitivity of rat kidney to both types of stimuli but caused a reduction in the responsiveness of the rabbit kidney to electrical stimuli only. Addition of flurbiprofen only slightly modified these results.
The results emphasize and confirm the fundamental difference in reactivity of the rat and rabbit kidney.
Bumetanide and frusemide, two ostensibly similar loop diuretics, show significantly different effects on these preparations suggesting that any modification by non‐steroidal anti‐inflammatory drugs cannot wholly be explained by similar PGE2 induced haemodynamic changes.
Influence of age, sex, pregnancy and protein‐calorie malnutrition on the pharmacokinetics of salicylate in rats
Authors: Varma D.R. , Yue T.L. 
Published: July 2012

The influence of age, sex, pregnancy and protein‐calorie malnutrition (PCM) on the plasma t1/2, plasma clearance (Clp) and apparent volume of distribution (Vd) of sodium salicylate (62 μmol kg−1) was determined in Sprague‐Dawley rats. Female and male rats of five different age groups (ages in weeks: pups 1, weanling 3, young 8–9, adult including pregnant 14–15, old 56–60) including three age groups with PCM (8–9, 14–15 and 56–60 weeks old) were used. Plasma and urinary salicylates were assayed by h.p.l.c.
Plasma 4 was longer and Clp smaller in pups than in weanling and young rats and comparable to values for old rats; Vd of salicylate in pups was larger than in any other group of rats. Plasma t1/2 was longer and Clp as well as Vd of salicylate were smaller in adult females than in males of comparable age. Relative to nonpregnant adult females, Vd of salicylate in pregnant rats was larger but plasma t1/2 and Clp were unchanged.
In all groups of rats studied, PCM decreased the plasma t1/2 and increased the Clp of salicylate; Vd was unchanged.
Changes in salicylate pharmacokinetics were not due to any differences in serum protein‐salicylate binding or to serum testosterone levels. Ovariectomy decreased the plasma t1/2 of salicylate but castration of male rats had no significant effect. Administration of testosterone to ovariectomized female rats exerted no significant effect on salicylate pharmacokinetics.
It is concluded that the physiological state and the nutritional status can modify salicylate pharmacokinetics; in so far as the rat model reflects the human situation, these variables should be taken into account for a rational salicylate therapy.
Does amiodarone affect heart rate by inhibiting the intracellular generation of triiodothyronine from thyroxine?
Authors: Lindenmeyer M. , Spörri S. , Stäubli M. , Studer A. , Studer H. 
Published: July 2012

The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3′ triiodothyronine (T3) was investigated. For this purpose we compared the effect of amiodarone with that of another potent inhibitor of the T4 → T3 conversion, i.e. the radiographic contrast medium iopanoic acid, on the heart rate of unanaesthetized guinea‐pigs.
Both amiodarone and, to an even greater extent, iopanoic acid induced an increase in serum 3.5′,3′ triiodothyronine (reverse T3), indicating effective inhibition of T4 → T3 conversion. Both amiodarone and iopanoic acid were accumulated in the liver and in the heart (measured as iodine).
While amiodarone induced bradycardia, iopanoic acid did not change the heart rate.
Supraphysiological amounts of exogenous T3 reverted the amiodarone induced bradycardia to near normal values. A comparable effect was observed with isoprenaline.
The intracellular inhibition of the T4 → T3 conversion is not the ultimate mode of the action of the amiodarone effect on heart rate. It is thought that amiodarone interacts with T3 at its receptor or somewhere later along the pathway from the T3‐receptor interaction to the final effect of T3 on heart rate.
Prostaglandins and thromboxane in the delayed phase of shock induced by Serratia marcescens endotoxin
Authors: Parratt J.R. , Sharma N. , Zeitlin I.J. 
Published: July 2012

The cardiovascular and metabolic effects of an endotoxin derived from Serratia marcescens were examined in anaesthetized, spontaneously‐breathing cats. There was a marked initial elevation of right atrial pressure (the result of pulmonary vasoconstriction) and decreases in systemic arterial pressure and in arterial PO2.
The ‘delayed’ effects of endotoxin shock in this species (1–8 h) consisted of a reduced cardiac output and decreased urinary excretion. Blood pressure and myocardial contractility (assessed from measurement of left ventricular (LV) dP/dt and LV end‐diastolic pressure) were maintained throughout this phase. There was evidence of a metabolic (lactic) acidosis largely compensated by hyperventilation.
Plasma levels (both arterial and mixed venous blood samples) of prostaglandin (PG)E2, PGF2α, 6‐keto PGF1α and thromboxane (TX)B2 were measured by radioimmunoassay techniques. Endotoxin administration caused substantial increases in the plasma levels of all four derivatives of arachidonic acid, especially between 1 and 6 h.
Separation of the endotoxin‐treated cats into survivors and non‐survivors showed that the non‐survivors had significantly higher circulating levels of PGE2, TXB2 and PGF2α. It is suggested that TXB2 and PGF2α might contribute to some of the detrimental effects of endotoxin (e.g. pulmonary, mesenteric, renal vasoconstriction; platelet aggregation with resulting organ failure) and that prostacyclin may be beneficial in endotoxin shock in this species.
The dependence of excitatory junction potential amplitude on the external calcium concentration in narcotic tolerant mouse vas deferens
Authors: Einstein R. , Lavidis N. A. 
Published: July 2012

The dependence of neurotransmitter secretion on external calcium ions during development of opiate tolerance in the mouse vas deferens was studied.
The writhing response of mice to an i.p. injection of acetylcholine was inhibited by morphine. Reversal of this antinociceptive effect of morphine during chronic treatment signalled the development of tolerance.
Tolerance to morphine at the neuromuscular junction was shown as a reversal of the initial shift of the size of the excitatory junction potential (e.j.p.) vs extracellular calcium concentration relationship back towards the control without any change in the power of 2.4.
Facilitation in the amplitude of the e.j.p. occurs with low frequency (2 Hz) stimulation. The initial increase in facilitation induced by morphine was reversed by chronic morphine treatment without any change in the plateau e.j.p. amplitude achieved after a long low frequency train of impulses.
At high frequencies (10 Hz) the initial increase in e.j.p. amplitude was followed by a depression. Acute morphine administration decreased the size of the e.j.p., this was followed by an increase in facilitation and a decrease in depression. These effects were reversed after chronic morphine treatment.
Tolerance to morphine involves a counteradaptive process which restores the normal entry of calcium ions or its actions within the release sites in promoting transmitter release.
Prejunctional dopamine receptors modulate twitch responses to parasympathetic nerve stimulation in the rabbit isolated rectococcygeus muscle
Authors: Drew G.M. , Hilditch A. 
Published: July 2012

Field stimulation of the parasympathetic nerves supplying the rabbit isolated rectococcygeus muscle produced individual twitch responses that were inhibited by dopamine (1 × 10−8−1 × 10−5M).
The twitch‐inhibitory effect of dopamine was reversed by haloperidol or sulpiride (1 × 10−8 − 1 × 10−5M for either) but not by phentolamine or yohimbine (up to 1 × 10−4M). Haloperidol and sulpiride were potent, specific, competitive antagonists of the twitch‐inhibitory effect of dopamine; their pA2 values were 8.39 and 7.75, respectively. In contrast, cis α‐flupenthixol, fluphenazine, bulbocapnine and thioridazine were weak or inactive against dopamine.
Concentrations of dopamine that inhibited the twitch response to parasympathetic nerve stimulation had little or no effect on contractions elicited by carbachol or by direct muscle stimulation after abolition of neuronal conduction by tetrodotoxin. Thus, the effects of dopamine on responses elicited by parasympathetic nerve stimulation seem to be exerted at a prejunctional level rather than directly on the smooth muscle.
The twitch‐inhibitory effect of dopamine was mimicked by epinine, N,N‐diethyldopamine, N,N‐di‐n‐propyldopamine, 5,6‐ADTN, N,N‐di‐n‐propyl 5,6‐ADTN, 6,7‐ADTN, apomorphine and Sandoz 27–403. Sulpiride reversed the effects of all these agonists.
N,N‐di‐n‐propyl‐6,7‐ADTN and SK & F 82526 also inhibited the twitch response but their effects were not reversed by sulpiride.
SK & F 38393 and DPI had little effect on the twitch response.
The pharmacological characteristics of the presynaptic dopamine receptors in the rabbit rectococcygeus muscle show that they resemble those in the cat heart and rabbit ear artery in some respects but there are differences that suggest that the presynaptic dopamine receptors in the rabbit rectococcygeus muscle constitute a specific subgroup of receptors.
Effects of reduced calcium ion concentration and of diltiazem on vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation in rat isolated tail artery
Authors: Medgett Iain C. , Rajanayagam M. A. Sharmini 
Published: July 2012

In isolated, perfused proximal segments of Sprague‐Dawley rat tail artery, idazoxan (100 nmoll1) displaced the concentration‐response curve to noradrenaline (NA) to the right. The log shift of the NA concentration‐response curve was greater at lower concentrations than at higher concentrations of NA. Idazoxan (100 nmoll−1) had no effect on responses to electrical stimulation.
Prazosin (10 nmoll−1) displaced the concentration‐response curve to NA to the right as well as markedly reducing responses to sympathetic nerve stimulation.
The concentration‐response curve to NA, obtained after reducing the concentration of calcium ions in the Krebs solution from 2.5 to 0.6 mmoll−1, was significantly displaced to the right. Responses to sympathetic nerve stimulation were not affected by this reduction in the concentration of calcium ions.
Diltiazem (1 and 10 μmoll−1) significantly displaced the concentration‐response curve to NA to the right but had no effect on sympathetic nerve stimulation.
These in vitro results in peripheral arterial smooth muscle confirm the findings of previous in vivo studies which suggest that α2‐adrenoceptors contribute to the vasoconstrictor responses elicited by α‐adrenoceptor agonists and that these responses but not those mediated by α1‐adrenoceptors are dependent on extracellular calcium.
The in vitro pharmacology of xamoterol (ICI 118,587)
Authors: Malta E. , Mian M. Aqleem , Raper C. 
Published: July 2012

The effect of xamoterol and (‐)‐isoprenaline have been compared for their activity at β‐adrenoceptor sites in a number of in vitro cardiac and smooth muscle preparations.
Xamoterol produced weak positive chronotropic effects in guinea‐pig, rat and cat atria (intrinsic activity < 0.55, (‐)‐isoprenaline = 1). Positive inotropic effects were obtained in driven left atria of the cat but were absent in guinea‐pig left atrial and right ventricular strip preparations. Agonistic effects were due to β1‐adrenoceptor stimulation.
Xamoterol was without β‐adrenoceptor‐mediated inhibitory effects in guinea‐pig ileal, tracheal and uterine preparations and in the rat vas deferens and oestrogen‐primed uterus. Weak β2‐adrenoceptor‐mediated relaxation was obtained in progesterone‐primed rat uteri.
Xamoterol produced non‐specific inhibitory effects in guinea‐pig ileal and tracheal preparations.
Xamoterol acted as a competitive antagonist at βr (pA2 range = 7.4 to 7.8) and β2‐adrenoceptors (pA2 range 5.2 to 6.2) and displaced [125I]‐iodocyanopindolol from guinea‐pig left atrial (pKD = 7.25) and uterine (pKD 5.24) membrane preparations.
It is concluded that xamoterol displays a selective affinity for β1‐adrenoceptors. Although its partial agonistic actions are more evident at β1‐adrenoceptor sites, like prenalterol, xamoterol displays a degree of tissue rather than receptor‐dependent selectivity.
Forskolin: its effects on potassium‐evoked release of vasopressin from the rat neurohypophysis
Authors: Bowman David , Hope Derek B. 
Published: July 2012

The effect of forskolin, added either before or 5 min after the onset of potassium‐evoked release of vasopressin from isolated neurointermediate lobes of the rat has been investigated.
A low concentration of forskolin (1 μM), added before stimulation, enhanced the potassium‐evoked release of vasopressin throughout two successive 5 min periods of stimulation. Higher concentrations of forskolin (10–80 μM) produced no effect on the potassium‐evoked release of hormone during the first 5 min of stimulation, but inhibited release during the second 5 min period.
When added 5 min after the onset of potassium stimulation, forskolin (1–80 μM) reduced the amount of vasopressin released during the remaining 5 min of stimulation.
Forskolin produced a concentration‐dependent increase in cyclic AMP during both the control and potassium stimulation periods.
The amount of cyclic AMP generated by forskolin during potassium stimulation was less than that produced during the corresponding control periods.
The effects of a new opioid analgesic, meptazinol, on the respiration of the conscious rat
Authors: Cowlrick I.S. , Shepperson N.B. 
Published: July 2012

In the conscious rat arterial PCO2 was measured as an index of respiratory status.
The opioid analgesic meptazinol (7.5–30 mg kg−1) evoked small but significant increases in arterial PCO2 which were attenuated by naloxone.
Meptazinol significantly reduced the increase in arterial PCO2 evoked by morphine.
The respiratory depression induced by meptazinol, but not that induced by morphine, was enhanced by pretreatment with atropine.
The (+)‐enantiomer, but not the (‐)‐enantiomer of meptazinol increased arterial PCO2. In contrast, only the (‐)‐enantiomer reduced the respiratory depressant effect of morphine.
It is proposed that the degree of respiratory depression induced by meptazinol is limited by its opioid antagonist and cholinomimetic properties.
Role of putative neurotransmitters in the central gastric antisecretory effect of prostaglandin E2 in rats
Authors: Puurunen Juhani 
Published: July 2012

The role of putative neurotransmitters of the central nervous system in the central gastric antisecretory effect of prostaglandin E2 (PGE2) was investigated in pylorus‐ligated rats.
Pretreatment of the rats with an intracerebroventricular (i.c.v.) injection of 6‐hydroxydopamine (6‐OHDA) prevented the antisecretory effect of the i.c.v. administration of PGE2, whereas pretreatment with 5,6‐dihydroxytryptamine (5,6‐DHT) plus p‐chlorophenylalanine (PCPA) had no effect.
I.c.v.‐administered phentolamine and idazoxan antagonized the inhibition of gastric secretion induced by i.c.v. PGE2, whereas prazosin, propranolol and sulpiride injected via the same route were ineffective.
Diphenhydramine, cimetidine, naloxone and theophylline, all administered i.c.v., did not modify the antisecretory effect of i.c.v. PGE2.
The results suggest that an activation of α2‐adrenoceptors in the brain is involved in the central gastric antisecretory effect of PGE2, whereas neither central 5‐hydroxytryptamine receptors, α1‐ or β‐adrenoceptors, D2‐dopamine receptors, histamine or opioid receptors nor adenosine seem to play any role here.