bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF ISOPRENALINE AND PHENYLEPHRINE ON THE ADENOSINE 3′,5′‐MONOPHOSPHATE CONTENT AND MECHANICAL ACTIVITY OF COLD‐STORED AND FRESH TAENIA CAECUM FROM THE GUINEA‐PIG
Authors: HONDA F. , KATSUKI S. , MIYAHARA J.T. , SHIBATA S. 
Published: July 2012

1 Cold storage treatment of the guinea‐pig taenia caecum had a greater inhibitory effect on the isoprenaline‐induced relaxation than that induced by phenylephrine. Prolonged cold storage (12‐14 days) almost abolished the effect of isoprenaline but only reduced the phenylephrine effect. The ED50 of cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) that elicited muscle relaxation was not altered by the prolonged cold storage.2 After cold storage treatment, tissue cyclic AMP content was decreased; however, isoprenaline still caused a dose‐dependent increase in the cyclic AMP level. The threshold dose of isoprenaline for cyclic AMP accumulation was the same in fresh and cold‐stored preparations.3 In the fresh preparation, the onset of the isoprenaline (10−6 M)‐induced relaxation preceded the increase in tissue cyclic AMP.4 Isoprenaline, phenylephrine, adrenaline and noradrenaline at doses (ED50) sufficient to induce muscle relaxation did not always increase the cyclic AMP level.5 Similarly, the responses to papaverine and nitroglycerine were not accompanied by an increase in cyclic AMP.6 The adenylate cyclase and phosphodiesterase (low and high Km) activities of taenia caecum were not attenuated by the prolonged cold storage.7 Propranolol inhibited both the isoprenaline‐induced relaxation and cyclic AMP accumulation; however, the pA2 values were significantly different for the two events.8 Based on these results, both the relaxation and cyclic AMP accumulation caused by isoprenaline are mediated by activation of β‐adrenoceptors but are independent phenomena.
THE EFFECT OF ANGIOTENSIN I CONVERTING ENZYME INHIBITOR (SQ 20881) ON THE RELEASE OF PROSTAGLANDINS BY RABBIT KIDNEY, in vivo
Authors: JOHNS E. J. , MURDOCK R. , SINGER BERTHA 
Published: July 2012

1 Prostaglandin E‐ and F‐like material has been estimated in renal venous blood of the left kidney of anaesthetized rabbits following renal nerve section. Prostaglandins were estimated by bioassay following solvent extraction and column chromatography.2 Electrical stimulation of the renal nerves of the left kidney to reduce renal blood flow by approximately 15% for 15 min resulted in a significant increase in the concentration of prostaglandin E‐like material in the renal venous blood. The peak values were normally seen either in the last 5 min of the stimulation period or in the first 5 min after the end of the stimulation period. The concentration of prostaglandin F‐like material was not significantly altered.3 Similar reduction of renal blood flow of the left kidney by renal artery constriction also resulted in a significant increase in the concentration of prostaglandin E‐ but not F‐like material in renal venous blood. The timing and magnitude of the response was comparable with that observed with renal nerve stimulation.4 The effect of an angiotensin I converting enzyme inhibitor, SQ 20881, on the response to both renal nerve stimulation and renal artery constriction has been studied. The administration of the drug did not significantly reduce the release of prostaglandins from the denervated kidneys, however, the increase in prostaglandin E‐like material, in response to both stimuli, was abolished.5 The results suggest that the increase in prostaglandin E‐like material released from the kidney in response to low frequency stimulation or to modest reductions in renal blood flow is dependent on the release of renin and that the effect is mediated by the formation of angiotensin II and not angiotensin I.
THE MECHANISM OF ACTION OF NARCOTIC ANALGESICS IN THE GUINEA‐PIG ILEUM
Authors: NORTH R.A. , TONINI M. 
Published: July 2012

Intracellular recordings were made from neurones in the myenteric plexus of the guinea‐pig ileum. Single myenteric ganglia were maintained in vitro and drugs were applied by adding them to the perfusing solution.
Narcotic analgesics hyperpolarized the membrane of a proportion of neurones in the myenteric plexus.
The membrane hyperpolarization was sometimes associated with a decrease in input resistance. These effects reduced the excitability of myenteric neurones.
The effects of narcotics occurred at low concentrations (10 nM to 1 μM), were stereospecific and were reversed by naloxone.
It is proposed that the morphine‐sensitive neurones may be the cholinergic efferents to the muscle layers. By hyperpolarizing these neurones, morphine may prevent their excitation by electric field stimulation. This may explain why narcotic analgesics reduce the output of acetylcholine and the contractile response of this preparation when it is excited by field stimulation.
DIURETICS AND THE RENAL ADENYLATE CYCLASE SYSTEM
Authors: DAWBORN J.K. , MACNEIL S. , MARTIN T.J. 
Published: July 2012

The relationship between the diuretic effectiveness and the effect on the renal adenylate cyclase of three diuretics, acetazolamide, frusemide and ethacrynic acid, was examined. The hypothesis that acetazolamide and parathyroid hormone (PTH), inhibit renal carbonic anhydrase by a cyclic adenosine 3′,5′‐monophosphate (cyclic AMP)‐dependent mechanism was also tested.
In vitro, acetazolamide, frusemide and ethacrynic acid at high concentrations (10−3M) all produced some inhibition of basal and stimulated rat kidney plasma membrane adenylate cyclase. The effect of acetazolamide was much less than that of frusemide and ethacrynic acid. These plasma membrane effects were reproduced in studies of cyclic AMP formation in isolated kidney tubules of rats.
Intravenous injections of acetazolamide did not change the total cyclic AMP content of the kidneys of rats killed by microwave irradiation.
Acetazolamide produced a diuresis in the rat and a slight inhibition of the antidiuretic effect of Pitressin. Frusemide produced a diuresis and greatly reduced the antidiuretic response to Pitressin. Ethacrynic acid was ineffective as a diuretic in the rat and actually enhanced the antidiuretic response to Pitressin.
In investigating the possible influence of diuretics and PTH on the activity and state of phosphorylation of carbonic anhydrase it was found that: there was no correlation between the ability of diuretics to inhibit carbonic anhydrase activity and to inhibit carbonic anhydrase phosphorylation; neither PTH nor cyclic AMP (in the presence of adenosine triphosphate, Mg2+, K+ and incubation at 37°C) inhibited rat cortex homogenate carbonic anhydrase activity.
It seems unlikely that any of the tested diuretics exerts its pharmacological effect by means of changes in kidney cyclic AMP metabolism.
A COMPARISON IN RABBIT ISOLATED HEARTS OF THE DYSRHYTHMOGENIC POTENTIAL OF AMITRIPTYLINE, MAPROTILINE AND MIANSERIN IN RELATION TO THEIR ABILITY TO BLOCK NORADRENALINE UPTAKE
Authors: HARPER BARBARA , HUGHES I.E. 
Published: July 2012

In isolated hearts of rabbits, perfusion with (‐)‐noradrenaline (0.0059 to 5.9 μM) resulted in chronotropic and inotropic responses and a shortening of the interval between peak atrial and peak ventricular tensions (the A‐V contraction interval). No dysrhythmias developed but at higher concentrations (590 μM) 2 out of 7 hearts developed dysrhythmias (extrasystoles).
Perfusion with the antidepressants amitriptyline or maprotiline (4.8 μM) or mianserin (28.8 μM) reduced ventricular force, did not change heart rate and only amitriptyline reduced atrial force and lengthened the A‐V contraction interval. At 4.8 μM mianserin produced only a marginal shortening of the A‐V contraction interval.
At these concentrations no dysrhythmias developed but at higher concentrations (amitriptyline 8 μM. maprotiline 8 μM, mianserin 60 μM) all the agents produced dysrhythmias involving an interference with atrio‐ventricular synchronization.
In the presence of mianserin (4.8 μM) perfusion with noradrenaline (0.0059 to 5.9 μM) shortened the A‐V contraction interval and did not produce dysrhythmias. In the presence of amitriptyline or maprotiline (4.8 μM) or mianserin (28.8 μM) the A‐V contraction interval generally lengthened and most hearts developed dysrhythmias (usually involving interference with atrio‐ventricular synchronization).
[3H]‐(‐)‐Noradrenaline uptake in perfused rabbit hearts and in mouse isolated atria or vasa deferentia was inhibited by the antidepressants to a similar extent, amitriptyline being marginally most potent (molar potency taken as 1.0), maprotiline being less potent (1.5) and mianserin least potent (2.0).
It is concluded that of these three antidepressants, mianserin is least cardiotoxic in this preparation and that the ability of these antidepressants to predispose to noradrenaline‐induced dysrhythmias is not related to blockade of noradrenaline uptake.
THE EFFECTS OF PROSTAGLANDIN E1, BRADYKININ AND HISTAMINE ON CANINE SYNOVIAL VASCULAR PERMEABILITY
Authors: GRENNAN D.M. , MITCHELL W. , MILLER W. , ZEITLIN I.J. 
Published: July 2012

The relative effects of prostaglandin E1, bradykinin and histamine on canine synovial vascular permeability were investigated by a method based on the measurement of the amounts of radiolabelled dextran (molecular weight 20,000) leaking from the circulation into the synovial cavity.
Bradykinin, prostaglandin E2 and histamine in that order of potency all increased synovial vascular permeability. Threshold concentrations were 0.3 μM, 3 μM and 30 μM respectively.
The effects of infusion of prostaglandin E1 combined with either bradykinin or histamine were greater than mere summation.
DOPAMINE‐INDUCED DEPRESSION OF ADRENERGIC NERVE‐MEDIATED CONTRACTION OF SMOOTH MUSCLE
Authors: BELL C. , MATALANIS G. 
Published: July 2012

Dopamine (0.25‐1.0 μM) applied extraluminally depressed vasoconstrictor responses of the perfused rabbit ear artery to low frequency adrenergic nerve stimulation.
The depressant effect of dopamine was prevented in the presence of haloperidol (0.1 μM) but not in the presence of phentolamine (0.03‐0.14 μM).
Extraluminal dopamine (1 μM) or intraluminal injection of dopamine in amounts up to 0.025 %mumol had no dilator effect on arteries partially constricted by infusion of noradrenaline.
Dopamine also depressed contractile responses of guinea‐pig vas deferens to low frequency adrenergic nerve stimulation. However, in this tissue the effect of dopamine was prevented by phentolamine but not affected by haloperidol.
In neither the rabbit ear artery nor the guinea‐pig vas deferens did haloperidol increase the magnitude of responses to nerve stimulation or affect muscle sensitivity to noradrenaline.
We conclude that the adrenergic axons in the rabbit ear artery, but not the guinea‐pig vas deferens, possess specific receptors for dopamine whose activation depresses axonal conduction or transmitter release. However, our results do not favour the view that these receptors are activated during normal transmission at physiological frequencies.
THE EFFECT OF MAGNESIUM ON THE RESPONSE OF SMOOTH MUSCLE TO 5‐HYDROXYTRYPTAMINE
Authors: GOLDSTEIN S. , ZSOTÉR T.T. 
Published: July 2012

The responses to 5‐hydroxytryptamine (5‐HT) of rabbit isolated mesenteric artery and vein and longitudinal smooth muscle of guinea‐pig ileum were examined in Krebs solution containing 0, 1.2 or 2.4 mm Mg2+.
When the concentration of Mg2+ was raised the spontaneous contractile activity of rabbit mesenteric vein was depressed. The responses to 5‐HT in rabbit mesenteric artery and vein and guinea‐pig ileum were greater in the absence of Mg2+. The initial fast component of 5‐HT‐induced contractions in rabbit mesenteric vein was reduced more consistently than the subsequent slow component by increasing the Mg2+ concentration.
Exposure of mesenteric vein to Ca‐free solution containing ethyleneglycoltetra‐acetic acid (EGTA) promptly abolished 5‐HT contraction in normal‐Mg but not in low‐Mg Krebs solution.
In mesenteric veins, no difference was observed in either the ‘lanthanum‐resistant’ uptake of 45Ca or total tissue Ca, measured by atomic absorption spectrophotometry, after 60 min exposure to either low‐Mg or normal‐Mg Krebs solution. On the other hand, after 5 min exposure, the ‘lanthanum‐resistant’ uptake of 45Ca was greater in the absence of Mg2+ than in the presence of higher Mg2+ concentrations.
It is suggested that Mg2+ depressed the 5‐HT response at least partly by reducing the availability of Ca2+ from a rapidly equilibrating intracellular pool.
BIOCHEMICAL EVIDENCE FOR THE DUAL ACTION OF LABETALOL ON α‐ AND β‐ADRENOCEPTORS
Authors: AGGERBECK MARTINE , GUELLAEN GEORGES , HANOUNE JACQUES 
Published: July 2012

Labetalol (AH 5158A) inhibited the adrenaline‐stimulated adenylate cyclase activity of rat liver and heart. This drug had no effect on basal or guanosine triphosphate (GTP)‐activated adenylate cyclase activities.
Labetalol displaced the binding of the specific ligands [3H]‐dihydroergocryptine and (—)‐[3H]‐dihydroalprenolol from their respective α and β‐adrenoceptors in rat heart and liver. The affinity of labetalol was 10 fold higher for the β‐ than for the α‐adrenoceptor. It appeared to be 10 to 100 times less potent than phentolamine in blocking α‐adrenoceptors and 5 to 10 times less potent than propranolol in blocking β‐receptors.
It is concluded that labetalol exerts its dual α‐ and β‐antagonism by acting directly on the plasma membranes, where it binds competitively to α‐ and β‐adrenoceptors.
INHIBITION OF [3H]‐DIHYDROALPRENOLOL BINDING TO RAT CARDIAC MEMBRANES BY VARIOUS β‐BLOCKING AGENTS
Authors: CHENIEUX‐GUICHENEY P. , DAUSSE J.P. , MEYER P. , SCHMITT H. 
Published: July 2012

Binding of [3H]‐dihydroalprenolol ([3H]‐DHA) to rat cardiac membranes was rapid and reversible (fcj = 0.633‐0.701 × 106M_1 s_1 and fc_x = 0.0017‐0.0043 s_1).
[3H]‐DHA bound to a single class of binding sites with an equilibrium dissociation constant (Kd25°c) Of 5.7 ± 1.1 × 10−9M.
This binding was specific and the order of potency of adrenoceptor agonists in competing for the binding sites was (—)‐isoproterenol < (±)‐isoproterenol < (+)‐isoproterenol < (—)‐adrenaline < (—)‐noradrenaline. This was in agreement with the β1 nature of the cardiac β‐receptors.
Cardioselective β‐blockers (i.e. metoprolol, acebutolol and practolol) were shown to have lower binding site affinities, when compared to other blockers. This may be related to steric hindrance by the side‐chain at the aromatic end of these molecules.
VASODILATATION BY PROSTAGLANDIN F2α IN THE CANINE TONGUE THROUGH A PARASYMPATHETIC MECHANISM
Authors: SHIMIZU T. , TAIRA N. 
Published: July 2012

The vascular bed of the tongue in situ was perfused with blood through the lingual arteries at a constant pressure in anaesthetized dogs. All drugs except for SQ 14,225 were administered intra‐arterially.
Prostaglandin F2at (PGF2a) produced a dose‐dependent increase in blood flow through the lingual arteries (vasodilatation).
Marked desensitization was observed on the vasodilator “responses to repeated administration of PGF2a.
The vasodilator response to PGF2a was abolished by tetrodotoxin in doses that abolished the vasodilator response to electrical stimulation of the lingual nerve.
The vasodilator response to PGF2a was not affected by hexamethonium in doses that almost abolished the vasodilator response to lingual nerve stimulation.
The vasodilator responses to PGF2flt and to lingual nerve stimulation were scarcely modified by (‐)‐hyoscyamine in doses that fully antagonized the vasodilator response to acetylcholine.
Electrical stimulation of the vago‐sympathetic trunk and noradrenaline produced a decrease in blood flow through the lingual arteries.
These results indicate that the vasodilator response of the tongue to PGF2ae is due exclusively to excitation of parasympathetic postganglionic neurones and that neuronal receptors involved are quite distinct from nicotinic receptors.
Intravenous administration of SQ 14,225, an inhibitor of angiotensin I converting enzyme or kininase II, augmented the vasodilator responses to bradykinin and kallikrein but not that to lingual nerve stimulation.
The results suggest that neither kallikrein noukinin (including bradykinin) is responsible for the parasympathetically induced vasodilatation in the tongue.
UPTAKE AND INACTIVATION OF PROSTAGLANDIN E2 METHYL ANALOGUES IN THE RAT PULMONARY CIRCULATION
Authors: BAKHLE Y.S. , JANCAR SONIA , WHITTLE B.J.R. 
Published: July 2012

The fate of (15S)‐15‐methyl prostaglandin E2 methyl ester and 16,16‐dimethyl prostaglandin E2 in the pulmonary circulation of rat isolated lungs was compared with that of prostaglandin E2 by means of bioassay.
Calculated on the basis of height of response of the assay tissues, the inactivation of prostaglandin E2 was 96 ± 1%, of 15‐methyl prostaglandin E2 methyl ester, 53 ± 6% and of 16,16‐dimethyl prostaglandin E2, 50 ± 4%.
Responses of the hamster stomach strip to the prostaglandin E2 analogues passing through the pulmonary circulation were prolonged and slower in onset than those to the analogue given directly to the tissue. No such difference was observed with prostaglandin E2.
Bromocresol green, bromothymol blue, bromocresol purple and thymol blue (10−5 M) all inhibited the inactivation of the three prostaglandins studied, as did diphloretin phosphate (1.5 × 10−6 M). All five inhibitors also reversed the shape change in response seen after transpulmonary injection of 16‐16‐dimethyl prostaglandin E2.
We conclude that the inactivation of the methyl analogues is due to uptake, as they are not substrates for prostaglandin dehydrogenase.
The lung may act as a depot for some compounds taking them up from the pulmonary vessels and later releasing them slowly into the systemic circulation.
EVIDENCE FOR PURINERGIC INNERVATION OF THE ANOCOCCYGEUS MUSCLE
Authors: BURNSTOCK G. , COCKS T. , CROWE RAHIMA 
Published: July 2012

Fluorescence histochemical localization of quinacrine (which binds to adenosine 5′‐triphosphate (ATP)) revealed nerve fibres running singly and in bundles in both rat and rabbit anococcygeus muscle. Single neurone cell bodies and ganglia containing between 2 and 50 cells were also observed.
Catecholamine fluorescence studies revealed a dense adrenergic ground plexus, but no adrenergic ganglion cells were detected. No acetylcholinesterase‐positive nerve fibres or ganglion cells were seen in the rat.
When the tone was raised with guanethidine, a relaxation in response to field stimulation was revealed, which was unaffected by atropine but blocked by tetrodotoxin.
Release of ATP increased 3 to 6 times above background during stimulation of these non‐adrenergic, non‐cholinergic, inhibitory nerves.
Neither quinacrine staining nor the release of ATP during inhibitory nerve stimulation was affected by 6‐hydroxydopamine treatment, which abolished catecholamine fluorescence.
Exogenous ATP produced relaxation in high tone preparations of the rabbit anococcygeus muscle. ATP produced either contraction or a small relaxation followed by a contraction of the rat anococcygeus muscle, but treatment with low concentrations of the prostaglandin synthesis inhibitor indomethacin, converted the contraction to a relaxation.
These data are consistent with the view that the anococcygeus muscle is innervated by purinergic inhibitory nerves.
PHARMACOLOGY OF THE ADRENOCEPTORS AND CHOLINOCEPTORS OF THE BC3HI NONFUSING MUSCLE CELL LINE
Authors: MAUGER JEAN‐PIERRE , MOURA ANNE‐MARIE , WORCEL MANUEL 
Published: July 2012

We have studied the action of different transmitters on the transmembrane 42K or 86Rb efflux from tissue cultures of the BC3H1 muscle cell line.
The effect of catecholamines and carbachol (CCh) on the isotope efflux rate was measured by addition of the drugs at different times during the washout.
Noradrenaline (NA), phenylephrine (Phe), isoprenaline (Iso) and CCh increased 42K and 86Rb efflux rate in a dose‐dependent manner.
The action of NA seems to be due exclusively to the stimulation of α‐receptors, since its effect was blocked by phentolamine but not by propranolol. The effects of Iso on the 86Rb efflux were inhibited by propranolol. The β‐receptors in the BC3H1 cells seem to be of the β2‐type since they are stimulated by Iso and insensitive to NA.
The effect of CCh was blocked by (‐h)‐tubocurarine but not by atropine. This result confirms the presence of nicotinic receptors in BC3H1 cells.
CHANGES IN BLOOD FLOW AND MEDIATOR CONTENT OF RABBIT SKIN GRAFTS
Authors: LEWIS G.P. , MANGHAM BEVERLEY A. 
Published: July 2012

Blood flow changes have been measured in rabbit skin homografts and autografts and an attempt has been made to correlate these changes with the presence of vasoactive agents in homogenates of the grafts.
During the healing‐in of both types of grafts the blood flow and histamine content increased.
If this histamine was responsible for the vasodilatation via an H2‐receptor it must have been released in the form of ‘nascent’ or intrinsic histamine since the vasodilatation was not antagonized by antihistamine.
A peak of histamine concentration occurred in homografts, more than three times that in autografts at the onset of rejection. At the same time the blood flow stopped completely.
This vasoconstriction might be mediated by histamine since treatment with mepyramine delayed the cessation of blood flow from 5 days up to 7 to 10 days.
Prostaglandins appeared to be involved only in the period of peak blood flow in homografts because indomethacin did not delay the onset of rejection, but reduced the peak blood flow in the homografts at a time when there was an increased content of prostaglandin E2 in the homograft tissue.
FACTORS LIMITING THE RATE OF TERMINATION OF THE NEUROMUSCULAR BLOCKING ACTION OF FAZADINIUM DIBROMIDE
Authors: TYERS M.B. 
Published: July 2012

Reasons for the termination of the neuromuscular blocking action of fazadinium dibromide have been investigated.
In the anaesthetized cat, maximum neuromuscular block of tibialis anterior muscle twitches following rapid intravenous injection of fazadinium was obtained as the injection bolus passed through the muscle, indicating that fazadinium very readily crosses capillary membranes.
The half‐life of plasma clearance of fazadinium was about 1 min in both cat and man, despite a 10 fold difference in duration of action in these species. Plasma samples were bioassayed for neuromuscular blocking activity on an isolated, superfused phrenic nerve‐diaphragm preparation of the rat.
In the anaesthetized cat, occlusion of the renal or hepatic circulations did not prolong the neuromuscular blocking action of single doses of fazadinium. Repeated doses accumulated slowly when the hepatic circulation was occluded but not when the renal circulation was occluded.
Fazadinium is eliminated from the body by both the liver and kidneys but the rates of these processes are insufficient to account for the initial rapid plasma clearance.
The rate‐limiting step for the termination of the neuromuscular blocking action of fazadinium is most likely to be the rate of drug‐receptor dissociation.