bluuebunny/crossref_metadata_2025_split huggingface dataset:
A COMPARISON OF STEREOSPECIFICITY AT CENTRAL AND PERIPHERAL ‘MUSCARINE‐SENSITIVE’ ACETYLCHOLINE RECEPTORS: OBSERVATIONS WITH THE ENANTIOMERIC FORMS OF PROCYCLIDINE AND TRICYCLAMOL
Authors: BARLOW R.B. , DAWBARN D. , PYCOCK C.J. 
Published: July 2012

Procyclidine resembles hyoscine in enhancing the effects of amphetamine on ipsiversive turning by mice with a unilateral central dopamine lesion.
The stereospecific index for procyclidine is not greater than 10, in contrast to 173 for acetylcholine receptors in ileum from the same mice.
This suggests that although the central effects of procyclidine in this test involve acetylcholine receptors similar to those at peripheral sites, they cannot be identical with them unless there are differences at some secondary site, for example, if the weaker enantiomer were a stronger inhibitor of dopamine uptake or if there were a stereoselective uptake process for procyclidine itself.
THE EFFECTS OF AMILORIDE AND TRIAMTERENE ON URINARY MAGNESIUM EXCRETION IN CONSCIOUS SALINE‐LOADED RATS
Authors: DEVANE JOHN , RYAN MICHAEL P. 
Published: July 2012

The potassium‐sparing diuretics, triamterene and amiloride, reduced urinary magnesium excretion in conscious saline‐loaded rats.
Urinary magnesium‐conservation was also detected when amiloride was used in combination with the potent ‘loop‐blocking’ diuretic, frusemide.
EFFECT OF VARIOUS DOSES OF ACETYLSALICYLIC ACID IN COMBINATION WITH DIPYRIDAMOLE ON THE BALANCE BETWEEN PROSTACYCLIN AND THROMBOXANE IN HUMAN SERUM
Authors: VIINIKKA LASSE , YLIKORKALA OLAVI 
Published: July 2012

Thirty‐six healthy human subjects were randomly divided into six groups which were treated with a single dose of 75 mg (1.3 mg/kg) of dipyridamole alone, or 75 mg of dipyridamole in combination with 30 mg (0.5 mg/kg), 50 mg (0.8 mg/kg), 160 mg (2.6 mg/kg) and 330 mg (5.7 mg/kg) of acetylsalicylic acid (ASA), or with placebo.
The concentrations of prostacyclin (PGI2) and thromboxane A2 (TxA2) metabolites, 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α) and TxB2 respectively, were measured in serum with specific radioimmunoassays before and 1 and 3 h after the ingestion of the test dose.
The basal concentrations of 6‐keto‐PGF1α and TxB2 correlated significantly (r = 0.588, P < 0.001).
Dipyridamole alone did not change PGI2 or TxA2 production.
Dipyridamole‐ASA combinations with ASA doses between 0.5 and 0.8 mg/kg inhibited TxB2 production by 48 to 74%, and with the ASA doses between 2.6 and 5.7 mg/kg by about 90%. None of these combinations changed PGI2 production.
The ratio of 6‐keto‐PGF1α to TxB2 increased 3.5 to 6 times with ASA doses of 0.5 to 0.8 mg/kg and 21 to 29 times with doses between 2.6 to 5.7 mg/kg.
These results suggest that the anti‐thrombotic effect of dipyridamole in vivo is not mediated through direct changes in PGI2 and/or TxA2 production.
EFFECT OF LANTHANIDE IONS ON HISTAMINE SECRETION FROM RAT PERITONEAL MAST CELLS
Authors: PEARCE F.L. , WHITE J.R. 
Published: July 2012

Ions of the lanthanide series (lanthanum‐lutetium) inhibit histamine release induced by allergen and anti‐IgE in the presence of extracellular calcium. The inhibition is dose‐dependent in the range 10−6 to 10−9 m and there is no marked difference in potency between the lanthanides.
The response to lanthanum is biphasic and higher concentrations (10−4 m) potentiate the release. Maximal concentrations (10−3 m) again abolish secretion.
The effect of concanavalin A is weakly antagonized by lanthanum but strongly inhibited by higher lanthanides.
Inhibition of histamine release evoked by basic agents is markedly dependent on the ionic radius of the lanthanide. In the presence of extracellular calcium, dysprosium is the most effective inhibitor. Similar results are observed with dextran. In the absence of calcium, there is a regular increase in inhibition with decreasing ionic radius.
Inhibition of release in the presence of calcium is immediate and does not require preincubation with the lanthanide. The antagonism due to lanthanum is competitive and the pA2 values vary with the secretagogue. In contrast, the inhibitory effect in the absence of extracellular calcium increases progressively with time.
These results are discussed in terms of the calcium‐pools important in histamine release and the mode of action of different secretagogues.
COMPARATIVE ANTIDYSRHYTHMIC AND HAEMODYNAMIC EFFECTS OF ORALLY OR INTRAVENOUSLY ADMINISTERED MEXILETINE AND ORG 6001 IN THE ANAESTHETIZED RAT
Authors: MARSHALL R.J. , MUIR A.W. , WINSLOW E. 
Published: July 2012

The antidysrhythmic and haemodynamic effects of the aminosteroid, Org 6001, were studied in the rat anaesthetized with pentobarbitone. Mexiletine was used for comparison
Both Org 6001 (2–10 mg/kg) and mexiletine (1 mg/kg) given intravenously antagonized the development of dysrhythmias evoked by acute coronary artery ligation in rats
In antidysrhythmic doses, Org 6001 and mexiletine exerted only moderate and transient hypotension and depression of cardiac contractility (assessed from LV dP/dtmax). Org 6001 did, however, induce a more sustained bradycardia
Effective oral doses of Org 6001 (20–100 mg/kg) were similar to those of mexiletine, disopyramide and propafenone
Oral Org 6001 (100 mg/kg) was effective for 18 h whereas mexiletine (100 mg/kg) failed to protect against evoked dysrhythmias 3 h after dosing
Org 6001 and mexiletine differed in their actions on ventricular fibrillation threshold (VFT). Org 6001 (100 mg/kg orally 12 h before ligation) prevented the decrease in VFT produced by coronary ligation whereas mexiletine (100 mg/kg orally) had no effect. When administered intravenously, mexiletine (but not Org 6001) increased VFT in normal ventricular muscle.
INHIBITION BY APOMORPHINE OF THE POTASSIUM‐EVOKED RELEASE OF [3H]‐γ‐AMINOBUTYRIC ACID FROM THE RAT SUBSTANTIA NIGRA in vitro
Authors: ARBILLA SONIA , KAMAL LINDA A. , LANGER S.Z. 
Published: July 2012

The spontaneous and potassium‐evoked release of tritium from the rat substantia nigra prelabelled with [3H]‐γ‐aminobutyric acid [3H]‐GABA were assessed in vitro under conditions of supervision
Kainic acid lesions performed in the right caudate nucleus resulted in a 70% reduction in the ability of the homolateral nigral cells to take up and retain [3H]‐GABA when compared with the unlesioned side. The potassium‐evoked release of [3H]‐GABA remained proportional to the radioactivity retained in the tissue suggesting that the nigral GABA neurones that survived kainic acid treatment were still functional
The spontaneous outflow of [3H]‐GABA was significantly increased by exposure to different concentrations of exogenous GABA (10 to 1000 μM) when amino‐oxyacetic acid was present in the incubation medium
Apomorphine in concentrations ranging from 1 to 30 μM inhibited the calcium‐dependent release of [3H]‐GABA induced by 1 min exposure to 30 mM K+. These concentrations of apomorphine did not affect the spontaneous outflow of radioactivity. In vivo administration of haloperidol 0.2 mg/kg antagonized the in vitro inhibition by apomorphine of the K+‐evoked release of [3H]‐GABA
The results obtained with apomorphine and haloperidol suggest the presence of presynaptic dopamine‐like inhibitory receptors in gabaergic nerve terminals
Dopamine in concentrations ranging up to 300 μM did not modify either the spontaneous or the K+‐evoked release of [3H]‐GABA from the substantia nigra. These concentrations of dopamine effectively displaced [3H]‐dopamine recently taken up into the substantia nigra
Our results do not support the view that dendritic release of dopamine from the substantia nigra might be involved in the physiological modulation of the spontaneous or the stimulation‐evoked release of GABA.
THE EFFECT OF HARMINE ON THE ACTION POTENTIAL OF THE GUINEA‐PIG ATRIAL MUSCLE DEPENDS ON THE EXTERNAL CALCIUM CONCENTRATION
Authors: CARPENTIER ROBERT G. 
Published: July 2012

The influence of the external calcium concentration on the effect of harmine 2 × 10−5 M upon the guinea‐pig atrial muscle was analysed. Transmembrane potentials of contractile fibres were measured during exposure to the drug at 30°C
In preparations superfused with 1.35 mM Ca2+‐Tyrode solution and driven at 60/min (1Hz) harmine depressed the amplitude of the action potential (AP) and the maximum velocity of the upstroke (d V/dt). The resting potential was not affected. Harmine depressed similarly the d V/dt of fibres superfused with 2.7 mM Ca2+‐Tyrode solution but the AP was slightly enhanced
Harmine diminished both the AP and the d V/dt of fibres superfused with 2.7 mM Ca2+‐Tyrode solution and driven at a fast rate (180/min, 3 Hz). Increased external calcium concentration (5.4 mM) annulled the depressant effect on AP while the action on dV/dt persisted
It is concluded that the effect of harmine on the AP depends on the external calcium concentration. Increase [Ca2+]o reverses the depressant effect of harmine because it annuls the effect of the drug on the slow component of the upstroke. The action on the initial fast component of the rising phase of the action potential persists.
SELECTIVE INHIBITION OF THROMBOXANE BIOSYNTHESIS IN HUMAN BLOOD MONONUCLEAR CELLS AND THE EFFECTS ON MITOGEN‐STIMULATED LYMPHOCYTE PROLIFERATION
Authors: GORDON D. , NOURI A.M.E. , THOMAS R.U. 
Published: July 2012

The effects of six imidazole compounds were examined on thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) production and mitogen‐stimulated lymphocyte transformation in human blood mononuclear cells
UK 37248 (4‐(2‐[IH‐imidazol‐l‐yl]ethoxy)benzoic acid), imidazole and 1‐methylimidazole selectively inhibited TxB2 synthesis in a dose‐related manner, with corresponding increases in PGE2 production
Clotrimazole, benzimidazole and 2‐methylimidazole preferentially inhibited TxB synthesis but had little effect on PGE2 production
Clotrimazole and benzimidazole inhibited proliferative responses of the lymphocytes, but UK 37248 and 1‐methylimidazole did not affect transformation at concentrations which inhibited TxB2 synthesis to a similar level (over 90%)
The results do not support involvement of endogenous TxB2 in the process of lymphocyte mitogenesis or in the mechanism of the suppressive effects of some TxB2 synthetase inhibitors.
EFFECTS OF A SALT OF CHOLESTYRAMINE AND 2‐[4‐(p‐CHLOROBENZOYL)PHENOXY]2‐METHYL PROPIONIC ACID (α‐1081) ON BILIARY LIPID SECRETION IN RATS
Authors: ALDINI RITA , BARBARA LUIGI , BENELLI AUGUSTA , BORZATTA VALERIO , GEMINIANI STEFANIA , MASCELLANI GIUSEPPE , MORSELLI ANTONIO , RODA ALDO , RODA ENRICO 
Published: July 2012

Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile.
To evaluate this possible side‐effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of cholestyramine and 2‐[4‐(p‐chlorobenzoyl)‐phenoxy]2‐methyl propionic acid (α‐1081, 1.150 g/kg body wt., daily), cholestyramine (1.125 g/kgbody wt. daily), procetofenic acid (25 mg/kg body wt. daily) and saline respectively (six rats for each group).
Cholesterol saturation index significantly (P< 0.005) increased (from 0.21 ±0.01 to 0.39±0.09, mean±s.d.), in rats fed with procetofenic acid but it did not in α‐1081‐ and cholestyramine‐treated animals.
Procetofenic acid and, to a lesser extent, cholestyramine increased the bile flow. Procetofenic acid increased cholesterol secretion from 0.45±0.17 to 0.94 ± 0.19 μmol kg−1 body wt. h−1 (mean±s.d.).
Cholestyramine increased both serum cholesterol and bile acid secretion from 0.45±0.17 to 0.68±0.10 and 25.8±9.48 to 39.96 ± 6.68 μol kg−1 body wt. h−1 respectively; α‐1081, on the contrary, had no effect on bile lipid secretion.
These data suggest that α‐1081 may be used as a new hypolipidaemic drug without any risk of increasing cholesterol in bile.
RECEPTOR MECHANISMS FOR 5‐HYDROXYTRYPTAMINE IN RABBIT ARTERIES
Authors: BLACK J.L. , FRENCH R.J. , MYLECHARANE E.J. 
Published: July 2012

Previous investigations into the vascular actions of biogenic amines implicated in migraine have shown that the contractile effects of both 5‐hydroxytryptamine (5‐HT) and noradrenaline (NA) in the rabbit ear artery are mediated by a direct sympathomimetic action at α‐adrenoceptors, while in the rabbit aorta, 5‐HT and NA act on pharmacologically distinct receptors. The purpose of the present investigation was to determine whether the absence of 5‐HT receptors in rabbit ear arteries is characteristic of distributing arteries in general, or is confined to particular regional circulations.
Agonist‐antagonist interactions were studied in various rabbit vascular preparations (common carotid, external carotid and femoral arterial strips, and perfused ear arteries) by determining pA2 values for pizotifen and phentolamine against 5‐HT‐ and NA‐induced contractile responses.
In common carotid and femoral arteries, pizotifen was a potent competitive antagonist of 5‐HT, but weak against NA. The converse applied to phentolamine. In external carotid and ear arteries, pizotifen was a weak competitive antagonist of both 5‐HT and NA, whereas phentolamine was a potent competitive antagonist of both. Cocaine did not influence pA2 values against NA.
5‐HT and NA were of similar potency in common carotid and femoral arteries, but 5‐HT was much less potent than NA in external carotid and ear arteries.
The results indicate that rabbit common carotid and femoral arteries contain both D‐type 5‐HT receptors and α‐adrenoceptors, as does the aorta. However, external carotid arteries, like ear arteries, do not contain specific 5‐HT receptors. The action of 5‐HT in the external carotid artery is mediated by α‐adrenoceptors; this is a direct sympathomimetic action since it was not inhibited by cocaine or reserpine‐pretreatment.
6 The absence of 5‐HT receptors in the rabbit extracranial circulation may limit the usefulness of this species as a model for research relating to migraine.
CORRELATION BETWEEN CATECHOLAMINE RELEASE AND SODIUM PUMP INHIBITION IN THE PERFUSED ADRENAL GLAND OF THE CAT
Authors: GARCIA A.G. , GARCIA‐LOPEZ E. , MONTIEL C. , NICOLAS G.P. , SANCHEZ‐GARCIA P. 
Published: July 2012

Ca2+ re introduction to retrogradely perfused and ouabain (10−4M)‐treated cat adrenal glands caused a catecholamine secretory response which was greater the longer the time of exposure to the cardiac glycoside. Such a response was proportional to the external Na+ concentration [Na+]0.
A qualitatively similar, yet smaller response was observed when glands were perfused with Krebs solution lacking K+ ions; thus, K+ deprivation mimicked the secretory effects of ouabain. Catecholamine secretion evoked by Ca2+ reintroduction in K+‐free solution (0‐K+) was also proportional to [Na+]0 and greater the longer the time of exposure of the gland to 0‐K+ solution.
The ionophore X537A also mimicked the ouabain effects, since Ca2+ reintroduction to glands treated with this agent (25 μm) caused a sharp secretory response. When added together with X537A, ouabain (10−4m) did not modify the response to the ionophore.
N‐ethylmaleimide (NEM), another Na+, K+‐ATPase inhibitor, did not evoke the release of catecholamines; on the contrary, NEM (10−4m) inhibited the catecholamine secretory response to high [K+]0, acetylcholine, Ca2+ reintroduction and ouabain.
Ouabain (10−4 m) inhibited the uptake of 86Rb into adreno‐medullary tissue by 60%. Maximal inhibition had already occurred 2 min after adding the drug, indicating a lack of temporal correlation between ATPase inhibition and the ouabain secretory response, which took longer (about 30–40 min) to reach its peak. NEM (10−4 m) blocked 86Rb uptake in a similar manner.
The results are further evidence in favour of the presence of a Na+‐Ca2+ exchange system in the chromaffin cell membrane, probably involved in the control of [Ca2+]i, and in the modulation of catecholamine secretion. This system is activated by increasing [Na+]i, either directly (ionophore X537A, increased [Na+]0) or indirectly (Na+ pump inhibition). However, the simple inhibition of Na+ pumping does not always lead to a catecholamine secretory response; such is the case for NEM.
POTENTIATION OF K+‐EVOKED CATECHOLAMINE RELEASE IN THE CAT ADRENAL GLAND TREATED WITH OUABAIN
Authors: GARCIA A.G. , GARCIA‐LOPEZ E. , HORGA J.F. , KIRPEKAR S.M. , MONTIEL C. , SANCHEZ‐GARCIA P. 
Published: July 2012

A vigorous catecholamine secretory response was evoked by small increments (2–10 mM) of the extracellular concentration of K+ ([K+])0) in cat adrenal glands treated with ouabain (10−4m), and perfused with Krebs‐bicarbonate solution at room temperature.
The secretory response depends on [K+]0; increments of [K+]0 as small as 2 mM for 2 min evoked a clear secretory response; at 10–17.7 mM K+, the maximal secretory response was observed. In normal glands, not treated with ouabain, no increase of the rate of catecholamine output was observed by raising [K+]0 up to 17.7 mM for 2 min.
The K+ secretory response was time‐dependent, requiring at least 1 min to be initiated; on continued exposure to 10 mM [K+]0, the enhanced response remained for at least 1 h.
In low [Na+]0, the K+‐secretory response was unchanged. However, in 0‐Ca2+, high‐Mg2+ solutions, or in the presence of D600, an organic Ca2+ antagonist, it was abolished.
The K+‐induced secretory response was not altered in the presence of tetrodotoxin or tetraethylammonium.
It is concluded that ouabain potentiated the catecholamine secretory response to raised [K+]D by increasing the amount of Ca2+ available to the secretory machinery through (a) mobilization of an enhanced pool of membrane‐bound Ca2+, (b) activation of membrane Ca2+ inward current; or (c) decrease of intracellular Ca2+ buffering systems. The activation by ouabain of a membrane Na+‐Ca2+ exchange system is not involved in this K+‐secretory response. It is suggested that the plasma membrane ATPase enzyme system, by changing the affinity of its Ca2+ binding sites, might control the availability of this cation to the secretory machinery and, therefore, modulate catecholamine secretion in the adrenal gland.
STIMULATION OF RAT CEREBELLAR GUANOSINE 3‘,5’‐CYCLIC MONOPHOSPHATE (CYCLIC GMP) LEVELS: EFFECTS OF AMINO ACID ANTAGONISTS
Authors: FOSTER GEORGE A. , ROBERTS PETER J. 
Published: July 2012

The ability of glutamate, aspartate and related neuroexcitants to produce large calcium‐dependent increases in the levels of guanosine 3′,5′‐cyclic monophosphate (cyclic GMP) in immature rat cerebellar slices has been demonstrated.
These effects were inhibited by selective antagonist compounds, indicating the presence of at least two types of excitatory amino acid receptor mediating the cyclic GMP response.
Protoveratrine also produced large increases in cyclic GMP, and this action was antagonized by L‐glutamate diethylester suggesting that released endogenous glutamate, subsequently interacting with its postsynaptic receptors, is the predominant mechanism.
The kinetic characteristics of several of the inhibitor compounds were investigated.
MECHANISMS OF FORSSMAN‐INDUCED BRONCHOSPASM AND THEIR INHIBITION
Authors: BUTLER K.D. , SMITH J.R. 
Published: July 2012

The bronchospasm induced in the guinea‐pig by the injection of Forssman antiserum was biphasic in nature in both the sublethal and the lethal reaction.
The development of both phases of the bronchospasm in the sublethal reaction was dependent upon the presence of the intact complement system and circulating platelets. In the lethal reaction the phase II bronchospasm did not appear to depend on these factors.
The compounds used in this study inhibited phase I bronchospasm of the sublethal reaction in the order, methysergide > indomethacin > aspirin = sulphinpyrazone and phase II in the order, indo‐methacin > sulphinpyrazone > aspirin. Methysergide was inactive.
Aspirin, indomethacin and sodium salicylate all prevented the inhibitory action of sulphinpyrazone in reducing the phase II bronchospasm of the sublethal reaction in the order, indomethacin > sodium salicylate > aspirin, when the drugs were administered prior to sulphinpyrazone.
The inhibitory action of aspirin on the sulphinpyrazone effect could be prevented by administering sulphinpyrazone before aspirin. All drug‐induced inhibitions of sulphinpyrazone by aspirin, indomethacin and sodium salicylate were dose‐dependent.
COMPARISON OF THE EFFECTS OF METHOXAMINE WITH THOSE OF NORADRENALINE AND PHENYLEPHRINE ON SINGLE CEREBRAL CORTICAL NEURONES
Authors: BRADSHAW C.M. , PUN R.Y.K. , SLATER N.T. , SZABADI E. 
Published: July 2012

The technique of microelectrophoresis was used to compare the actions of methoxamine, noradrenaline and phenylephrine on single neurones in the somatosensory cerebral cortex of the rat.
Methoxamine evoked only excitatory responses on cortical neurones. The methoxamine‐sensitive cells were also excited by phenylephrine; cells excited by methoxamine could either be excited or depressed by noradrenaline.
Methoxamine appeared to be less potent than either noradrenaline or phenylephrine in evoking excitatory responses.
Responses to methoxamine had a slower time course than responses to either noradrenaline or phenylephrine, both the latencies to onset and the recovery times being longer for responses to methoxamine than for responses to noradrenaline or phenylephrine.
When the absolute mobilities of methoxamine, noradrenaline and phenylephrine were compared using an in vitro method, no significant differences were found between the mobilities of the three ionic species, suggesting that the three drugs have similar transport numbers. Thus the differences in potency between methoxamine and the other two drugs, and the difference between the time courses of responses to methoxamine and the other two drugs, are presumably of biological origin.
The α‐adrenoceptor antagonist, phenoxybenzamine, antagonized equally excitatory responses to methoxamine and noradrenaline, and responses to methoxamine and phenylephrine, without affecting responses to acetylcholine.
When responses to methoxamine and noradrenaline and responses to methoxamine and acetylcholine were summated on the same cells, the net responses were smaller than those expected on the basis of additive effects; the deviation from additivity was greater in the case of the summation of responses to methoxamine and noradrenaline than in the case of summation of responses to methoxamine and acetylcholine. This observation is consistent with the hypothesis that the interaction between methoxamine and noradrenaline follows the model of competitive dualism, whereas the interaction between methoxamine and acetylcholine follows the model of functional synergism.
The results suggest that methoxamine may act as a partial agonist at excitatory α‐adrenoceptors on cerebral cortical neurones.
EFFECTS OF PHOSPHATE‐MODIFIED ADENINE NUCLEOTIDE ANALOGUES ON INSULIN SECRETION FROM PERFUSED RAT PANCREAS
Authors: CHAPAL JEANNIE , LOUBATIERES‐MARIANI MARIE‐MADELEINE 
Published: July 2012

The effects of three methylene analogues of adenosine 5′‐triphosphate (ATP) or 5′‐diphosphate (ADP) have been studied on insulin secretion from the isolated perfused pancreas of the rat: 5′‐adenylmethylene diposphonate or β, γ‐methylene ATP, adenosine 5′‐α, β‐methylene triphosphate or α, β‐methylene ATP and adenosine 5′‐α, β‐methylene diphosphonate or α, β‐methylene ADP.
β.γ‐Methylene ATP did not elicit any increase of insulin release; α, β‐methylene ATP and α, β‐methylene ADP induced a biphasic stimulation of insulin secretion; this effect was dose‐related between 1.65 and 165 μmol/1. Relative potency ATP/α, β‐methylene ATP was 1.2 and ATP/α, β‐methylene ADP was 0.31.
Our results point to the importance of the steric and electronic characteristics of the polyphosphate chain of the analogues of ATP and ADP in inducing an insulin secretory effect. They support the hypothesis of a purine receptor for ATP and ADP.