bluuebunny/crossref_metadata_2025_split huggingface dataset:
A COMPARISON OF RATES OF DEPLETION AND RECOVERY OF NORADRENALINE STORES OF PERIPHERAL AND CENTRAL NORADRENERGIC NEURONES AFTER RESERPINE ADMINISTRATION: IMPORTANCE OF NEURONAL ACTIVITY
Authors: WAKADE ARUN R. 
Published: July 2012

The noradrenaline (NA) content of various peripheral sympathetic neuroeffector organs and brain was measured at various times after different doses of reserpine administered to the rat.
About a 25% reduction in the NA content of the heart was observed 24 h after 0.005 mg/kg reserpine. Two to ten times more reserpine was needed to obtain an approximately similar degree of depletion in the salivary gland and vas deferens; 0.1 mg/kg produced almost complete depletion in the heart and salivary gland, whereas 5 mg/kg was needed to deplete the vas deferens of its NA content.
The NA content of the brain and superior cervical ganglion was lowered by 20 to 30% in 24 h only when the reserpine dose was raised to 0.1 mg/kg, and 5 to 10 mg/kg was required to obtain over 95% depletion.
The rates of recovery of cardiac and salivary gland NA stores, after about 80 to 100% depletion by low and high doses of reserpine, were almost identical. About 50% restoration occurred in 7 to 15 days after a single dose of 0.1 mg/kg reserpine.
The superior cervical ganglion, the NA content of which was fully depleted by 10 mg/kg, showed almost complete recovery in about 7 days.
Transmural stimulation of the left atrium of the guinea‐pig for 30 min (5 Hz for 30 s/min), or exposure of the atrium to reserpine (5 μg/ml) for 30 min, caused modest but statistically insignificant reduction in tissue NA content. However, stimulation in the presence of reserpine 5 μg/ml for 30 min produced about 50% depletion of NA.
In vitro reduction in NA content caused by reserpine plus transmural stimulation, was even more pronounced after treatment of the isolated vas deferens of the rat with tetraethylammonium.
It is suggested that different rates of depletion following in vivo administration of reserpine are mainly due to variation in neuronal activity of different sympathetic neuroeffector organs.
REMOVAL OF INTERNALLY DEPOSITED GOLD BY 2,3‐DIMERCAPTOPROPANE SODIUM SULPHONATE (DIMAVAL)
Authors: GABARD B. 
Published: July 2012

Orally administered 2,3‐dimercaptopropane sodium sulphonate (DMPS, Dimaval) reduced the concentration of gold in rats treated with Auro‐Detoxin and increased the urinary excretion of the metal.
In a long‐term experiment, DMPS decreased significantly the concentration of gold in the kidneys and in the skin and increased it in plasma.
DMPS appears to be of interest as a possible antidote to gold, which could replace the more toxic 2,3‐dimercaptopropanol (BAL).
A NEW METHOD FOR STUDYING THE RELATIONSHIP BETWEEN HEPATIC UPTAKE OF DRUGS AND THEIR PHARMACODYNAMIC EFFECTS IN ANAESTHETIZED CATS
Authors: AGOSTON S. , HOUWERTJES M.C. , SALT P.J. 
Published: July 2012

A new in vivo experimental method is described whereby the liver can be temporarily excluded from the general circulation by means of a portocaval shunt operation. The influence of this manoeuvre upon the effects of pancuronium and Org 6368 was investigated using the tibialis muscle preparation of anaesthetized cats.
The procedure also allowed intraportal injections of the drugs to be made so that the effect of first‐passage uptake by the liver could be compared with hepatic exclusion in the same animal.
Hepatic exclusion greatly increased the duration of action of both drugs. Whereas intraportal injection did not significantly alter the effect of pancuronium on the tibialis muscle, the effect of Org 6368 was greatly diminished when given by this route.
The liver appears to tolerate short periods of hepatic exclusion and it is concluded that this technique may become a useful tool for studying the handling of drugs by this organ.
CHEMOKINESIS OF RAT POLYMORPHONUCLEAR LEUCOCYTES AND THE EFFECT OF CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE
Authors: BRADSHAW D. , GIROUD J.P. , ROCH‐ARVEILLER M. 
Published: July 2012

The chemotactic and chemokinetic properties of various substances were studied using rat polymorphonuclear leucocytes (PMN) in Boyden chambers.
Casein and the exudate from a carrageenan‐induced pleurisy possessed both chemotactic and chemokinetic properties, whereas erythrocyte lysates and albumin showed only chemokinetic activity.
Dibutyryl cyclic adenosine 3′,5′‐monophosphate (db cyclic AMP) had little or no effect on the migration towards casein and the inflammatory exudate, but stimulated the migration towards erythrocyte lysates and albumin.
It appears therefore that db cyclic AMP is able to increase a chemokinetic response initiated by other substances. The lack of effect of this compound on cell migration towards substances possessing both chemotactic and chemokinetic properties probably results from the equilibrating effect of a simultaneous stimulation of chemokinesis and inhibition of chemotaxis.
These results suggest that studies designed to investigate the effect of anti‐inflammatory drugs on cell migration should include the separate assessment of their ability to influence both chemotaxis and chemokinesis.
STRUCTURE‐ACTIVITY STUDIES ON AN EXCITATORY RECEPTOR FOR GLUTAMATE ON LEECH RETZIUS NEURONES
Authors: JAMES VICTORIA A. , WALKER R.J. , WHEAL H.V. 
Published: July 2012

Intracellular recordings were made from Retzius cells from the segmental ganglia of Hirudo medicinalis and Haemopis sanguisuga. Glutamate had a direct excitatory effect on the leech Retzius cells.
l‐Glutamate was 25 times more potent than d‐glutamate.
l‐Glutamate was approximately equipotent with ibotenic acid and 11.2 times more potent than l‐aspartic acid.
Quisqualic acid and kainic acid were both approximately 100 times more potent than l‐glutamate. dl‐1‐Amino‐cis‐1,3‐dicarboxycyclopentane was approximately 5 times more potent than l‐glutamate, while the trans isomer was 105 times less potent.
α‐NH2‐pimelic acid and β‐CH3‐glutamic acid reduced the response to l‐glutamate.
It is suggested that glutamic acid may interact with the Retzius cell glutamate receptor in an extended conformation.
RELATIONSHIP BETWEEN THE (−)‐[3H]‐DIHYDROALPRENOLOL BINDING TO β‐ADRENOCEPTORS AND TRANSMEMBRANE 86Rb EFFLUX OF THE BC3H1 NONFUSING MUSCLE CELL LINE
Authors: MAUGER JEAN‐PIERRE , WORCEL MANUEL 
Published: July 2012

We have studied the binding properties of the β‐adrenoceptor antagonist [3H]‐dihydroalprenolol ([3H]‐DHA) on a membrane preparation of the non‐fusing muscle cells BC3H1.
[3H]‐DHA appears to bind to two classes of sites. The first site has a high affinity (KD = 0.53 nm) and a low capacity (Bmax = 58 fmol/mg of protein). The second site has a low affinity (KD =110 nm) and a high capacity (Bmax = 1100 fmol/mg of protein).
The pharmacological properties of the high affinity low capacity site correspond to the known properties of the β2‐adrenoceptors since the agonists inhibit [3H]‐DHA binding following the series isoprenaline > adrenaline > noradrenaline > phenylephrine and the antagonists following the series alprenolol ≃ propranolol > butoxamine > practolol > phentolamine.
The binding properties of the β‐adrenoceptors were correlated with the effect of β‐adrenoceptor agonists and antagonists on 86Rb efflux rate from BC3H1 cells.
There is very good correlation between the dissociation constants obtained by inhibition of [3H]‐DHA binding by the antagonists alprenolol and propranolol, and the inhibition constants calculated from their antagonism of the 86Rb efflux rate stimulation by adrenaline. The ratio of the dissociation constants obtained by inhibition of [3H]‐DHA binding by agonists and their EC50, calculated from 86Rb efflux curves, is higher than 1. This high KD/EC50 ratio indicates a high coupling efficiency between receptor occupancy by agonists and the biological effect measured.
ACTIVE SITE‐DIRECTED ALKYLATION OF Na+‐K+‐ATPase BY DIGITALIS SULPHONATE DERIVATIVES OF DIFFERENT LIPOPHILICITY
Authors: FRICKE UWE , KLAUS WOLFGANG , ROGATTI MICHAEL 
Published: July 2012

Sulphonate derivatives of k‐strophanthidin and digitoxigenin were tested as active site‐directed labels of Na+‐K+‐adenosine triphosphatase (Na+‐K+‐ATPase) from guinea‐pig heart.
Lipophilicity ranged between P = 93 for strophanthidin‐3‐tosyloxy‐acetate (STA) and P = 3028 for digitoxigenin‐3‐tosyloxy‐acetate (DTA).
Although the alkylating moiety of STA and DTA was identical, the reversibility of Na+‐K+‐ATPase inhibition varied appreciably (82% and 35% respectively).
It is concluded that lipophilicity contributes considerably to the irreversible binding of alkylating cardiotonic steroids to myocardial Na+‐K+‐ATPase.
SOME in vitro AND in vivo ACTIONS OF THE NEW HISTAMINE H2‐RECEPTOR ANTAGONIST, RANITIDINE
Authors: DALY M.J. , HUMPHRAY JANET M. , STABLES R. 
Published: July 2012

Ranitidine has been investigated as an antagonist of the H2‐receptor‐mediated responses to histamine of guinea‐pig atrium and rat uterus in vitro and as an inhibitor of gastric acid secretion in the rat.
Ranitidine competitively antagonized histamine‐induced increases in contraction frequency of the guinea‐pig isolated right atrium. Ranitidine had a pA2 of 7.2 and was 7.9 and 4.5 times more potent than metiamide and cimetidine respectively.
Ranitidine competitively antagonized histamine‐induced relaxations of the rat isolated uterine horn. Ranitidine had a pA2 of 6.95 and was 3.6 and 5.9 times more potent than metiamide and cimetidine respectively.
Ranitidine, even at high concentrations, did not affect responses of the guinea‐pig isolated atrium or rat isolated uterus to (−)‐isoprenaline. Similarly it was without effect on either histamine or bethanechol‐induced contractions of guinea‐pig isolated ileum.
Ranitidine inhibited histamine‐ and pentagastrin‐induced gastric acid secretion in the perfused stomach preparation of the anaesthetized rat. Ranitidine was 5.2 and 7.0 times more potent on a molar basis than metiamide and cimetidine respectively, as an inhibitor of histamine‐induced gastric acid secretion.
It is concluded that ranitidine is a potent, competitive and selective antagonist of histamine at H2‐receptor sites and an effective inhibitor of gastric acid secretion in vivo.
SPURIOUS EFFECTS OF COMMERCIAL PREPARATIONS OF OXYTOCIN ON THE ISOLATED VAS DEFERENS OF THE RAT
Authors: BOTTING J.H. 
Published: July 2012

The inhibitory effect of a commercial preparation of oxytocin (Syntocinon) was studied on the isolated vas deferens of the rat.
The inhibition of contractions to agonists and to field stimulation obtained were mimicked by appropriate dilutions of chlorbutol, a preservative present in Syntocinon.
Preservative‐free synthetic oxytocin had no inhibitory effect on the tissue and slightly potentiated contractions evoked by field stimulation.
It is concluded that inhibitory effects of Syntocinon on the vas deferens are due to chlorbutol, not oxytocin.
INACTIVATION OF HERPES SIMPLEX VIRUS BY A PREGNENE DERIVATIVE (TX 3047)
Authors: PERBAL BERNARD 
Published: July 2012

Two strains of independently purified Herpes simplex virus type 1 were irreversibly inactivated after incubation with the pregnene derivative methyl‐p‐toluene sulphonate of diethylamino‐3‐β‐ethoxy‐20‐hydroxy‐pregn‐5‐ene (TX 3047) in vitro.
RNA and DNA synthesis (both cellular and viral) were studied in the presence of TX 3047. Viral and cellular DNA synthesis but not viral RNA synthesis was reduced.
Formation of infectious particles was not affected by TX 3047 if the parental virus was adsorbed to the cell before it was incubated with TX 3047. This suggests that TX 3047 acts at the level of the membrane.
PHARMACOLOGICAL CHARACTERIZATION OF THE EXCITATORY INNERVATION TO THE GUINEA‐PIG URINARY BLADDER in vitro: EVIDENCE FOR BOTH CHOLINERGIC AND NON‐ADRENERGIC‐NON‐CHOLINERGIC NEUROTRANSMISSION
Authors: KRELL ROBERT D. , McCOY JEAN L. , RIDLEY PETER T. 
Published: July 2012

Field stimulation of strips of guinea‐pig isolated urinary bladder with 5 s trains at 0.1 to 15 Hz resulted in frequency‐dependent, reproducible contractions.
At concentrations of 1 and 4× 10−7M and 1 × 10−6M, atropine produced a variable, partial inhibition of contractions at all frequencies but was most effective at frequencies of 3 Hz or more.
Tetrodotoxin (TTX), 5 × 10−7M, inhibited contractions at all frequencies by 80 to 90%.
Physostigmine, 2 × 10−6M, significantly enhanced the contractile response to frequencies of less than 10 Hz but did not enhance responses resistant to inhibition by atropine. Hexamethonium, 1 × 10−4M, slightly enhanced the contractile response to frequencies of 4 Hz or greater.
(±)‐Propranolol (5 × 10−6m), guanethidine (1 × 10−6m), phentolamine (5 × 10−6m) and clonidine (3 × 10−8m) each enhanced the contractile response to field stimulation.
Contractile responses obtained in the presence of atropine (4×10−7m) and guanethidine (1 × 10−6M) increased with time and were inhibited 60 to 80% by TTX (5 × 10−7m).
It is concluded that the cholinergic nervous system contributes, in part, to electrically‐induced excitatory contractions of the isolated urinary bladder of the guinea‐pig. Concomitant sympathetic stimulation appears to serve an inhibitory role. In addition, a major portion of the contractile response appears to be due to a non‐cholinergic non‐adrenergic, as yet unidentified, substance.
ELECTROMECHANICAL EFFECTS OF ANTHOPLEURIN‐A (AP‐A) ON RABBIT VENTRICULAR MUSCLE: INFLUENCE OF DRIVING FREQUENCY, CALCIUM ANTAGONISTS, TETRODOTOXIN, LIDOCAINE AND RYANODINE
Authors: KODAMA ITSUO , SHIBATA SHOJI , TOYAMA JUNJI , YAMADA KAZUO 
Published: July 2012

Anthopleurin‐A (AP‐A 5×10−9m, 1 × 10−8m) caused a prolongation of action potential duration (APD) and an increase of contractile force in rabbit isolated ventricular muscle preparations
The prolongation of APD and the positive inotropic effect of AP‐A (1 × 10−8m) were augmented by lowering the driving frequency from 2.0 to 0.2 Hz, resulting in an apparent negative staircase of contractile force in this frequency range. When the preparation was driven at an extremely low frequency (0.017 Hz), AP‐A did not increase the contractile force, but caused a considerable prolongation of APD
Verapamil (1 × 10−6m) and nifedipine (1 × 10−6m) had no apparent influence on the APD prolongation by AP‐A (5 × 10−9M, 1 × 10−8m). The positive inotropic effect of AP‐A was also relatively well maintained even in the presence of these calcium antagonistic drugs when the preparation was driven at a lower frequency (0.2 Hz)
Tetrodotoxin (TTX 2 × 10−6m) and lidocaine (1 × 10−4m) markedly inhibited both the APD prolongation and the positive inotropic effect of AP‐A (l×l 0−8 m)
In the presence of ryanodine (2 × 10−6m), an agent which is known to interfere with calcium release from the intracellular activator pool, AP‐A (l×l 0−8 m) failed to cause its positive inotropic effect in spite of the marked prolongation of APD
These results suggest that the effects of AP‐A on cardiac muscle are primarily mediated by the fast sodium inward current. Thus, delayed inactivation of sodium inward current may cause APD prolongation, and probably induces an alteration of intracellular calcium kinetics reflected by an increase of contractile force.
SEXUAL DIMORPHISM AND THE EFFECTS OF THE X‐LINKED Tfm LOCUS ON HEXOBARBITONE METABOLISM AND ACTION IN MICE
Authors: KING DOROTHY K. , SHAPIRO BERNARD H. 
Published: July 2012

Normal males of the testicular feminized strain of mice (Tfm) had longer hexobarbitone‐induced sleeping times than females, and hepatic hexobarbitone hydroxylase activity differed in that the Km was higher and the Vmax lower in the male
Castration and androgen replacement studies indicated that testicular androgens were responsible for the sexual differences in drug metabolism found in this mouse strain
Hepatic hexobarbitone metabolism and action were feminized in the intact, androgen‐insensitive, genetically male Tfm mouse. Furthermore, hexobarbitone hydroxylase activities were less responsive to large doses of testosterone in Tfm mice than in normal males
The Tfm mouse with a deficiency in androgen receptors responded to the enzyme‐inductive effects of phenobarbitone and softwood bedding, indicating that these inducers do not act through the androgen receptors.
EFFECTS OF AMILORIDE ON CONTRACTIONS AND THE RELEASE OF TRITIUM FROM RAT VAS DEFERENS PRELOADED WITH [3H]‐NORADRENALINE
Authors: AKHTAR‐KHAVARI FARZANEH , KHOYI M.A. , REZAEI EFFAT 
Published: July 2012

The effect of amiloride was studied on contractions and tritium release from rat vas deferens preloaded with [3H]‐noradrenaline
Amiloride had no effect on the resting tension and maximal contractile force of the vas deferens and did not alter the ED50 of noradrenaline
Amiloride (10−4‐10−3m) decreased the response of vas deferens to electrical stimulation dose‐dependently without inhibiting the response to KC1 (60 mm)
The effect of amiloride was not prevented by preincubation of the tissue with phentolamine, propranolol, atropine or indomethacin
Amiloride did not alter the spontaneous outflow of radioactivity from [3H]‐noradrenaline labelled vasa deferentia
Amiloride decreased the release of tritium induced by electrical stimulation or nicotine but did not inhibit the release of radioactivity induced by KC1 or tyramine. 7 It is concluded that amiloride may inhibit the contractions of rat vas deferens by inhibiting the release of noradrenaline.
THE EFFECTS OF MORPHINE AND METHIONINE‐ENKEPHALIN ON THE RELEASE OF PURINES FROM CEREBRAL CORTEX SLICES OF RATS AND MICE
Authors: STONE T.W. 
Published: July 2012

Slices of cerebral cortex from Wistar rats, TO mice or C57 mice were preincubated with [3H]‐adenosine, and labelled purines were subsequently released by electrical stimulation or by perfusing with ouabain, 100 μM
Electrically‐evoked purine release was substantially reduced when the Ca2+ concentration in the medium was lowered from 2.4 to 0.1 mM. In both rats and mice, the electrically‐evoked release was increased by morphine and methionine‐enkephalin (Met‐enkephalin), 10 μm and in rats and TO mice by morphine 1 μm, both drug effects being prevented by naloxone
Purine release evoked by ouabain was also increased by morphine 1 and 10 μm, though not by Met‐enkephalin, from slices of rat cortex. Ouabain‐induced release from TO mice was reduced by morphine, and from C57 mice was unchanged
The enhancement by morphine of electrically‐evoked purine release may indicate that purines mediate some effects of morphine in the CNS.
PRE‐ AND POSTJUNCTIONAL EFFECTS OF CLONIDINE‐ AND OXYMETAZOLINE‐LIKE COMPOUNDS IN GUINEA‐PIG ILEAL PREPARATIONS
Authors: MALTA E. , RAPER C. , TAWA PAULINE E. 
Published: July 2012

Noradrenaline and 28 imidazolidine (clonidine‐like) and imidazoline (oxymetazoline‐like) compounds with various phenyl ring substituents have been examined for their ability to inhibit responses to transmural stimulation and exogenous acetylcholine in ileal preparations from reserpine‐treated guinea‐pigs.
The bathing solution contained propranolol, mepyramine, cimetidine and desipramine to preclude interference with the responses by other than the α‐receptor‐mediated actions of the compounds.
In transmurally stimulated preparations the inhibitory response to noradrenaline is due to a combination of prejunctional α‐adrenoceptor stimulation and a postjunctional depressant effect that does not involve adrenoceptor activation.
Of the 28 imidazolidines and imidazolines studied, 21 inhibited transmurally elicited responses. In the various compounds studied this effect involved actions at pre‐ or postjunctional sites as indicated by (a) the frequency‐dependence of the inhibitory response, (b) its susceptibility to blockade by α‐receptor antagonists and (c) the relative concentrations required to inhibit responses to transmural stimulation and exogenous acetylcholine.
VESICULAR NORADRENALINE STORES IN PERIPHERAL NERVES OF THE RAT AND THEIR MODIFICATION BY TRANYLCYPROMINE
Authors: FILLENZ M. , STANFORD S.C. 
Published: July 2012

Vesicular noradrenaline stores were compared in the heart, salivary gland and vas deferens of the rat.
Noradrenaline storage vesicles in nerve terminals of different organs differed with respect to the amount of noradrenaline they contain in the endogenous store (content), the amount of exogenous noradrenaline they can take up from the circulation (uptake) and the amount of noradrenaline they contain when they are saturated (total storage capacity).
The data suggest that the vesicles in the salivary gland and vas deferens are almost completely filled with transmitter while, in the heart, the vesicular store is filled to only 55% of its total capacity.
The monoamine oxidase inhibitor, tranylcypromine, was found to increase not only the size of the endogenous store but also the size of the unfilled store.
PARTIAL AGONIST BEHAVIOUR OF ADENOSINE 5′O‐(2‐THIODIPHOSPHATE) ON HUMAN PLATELETS
Authors: CUSACK N.J. , HOURANI S.M.O. 
Published: July 2012

The effects of an adenosine diphosphate (ADP) analogue, adenosine 5′‐O‐(2‐thiodiphosphate) (ADP‐β‐S), in which a terminal phosphate oxygen has been replaced by sulphur, were studied on human platelets.
ADP‐/3‐S induced platelet aggregation and inhibited prostaglandin E 1 (PGE 1)‐stimulated adenylate cyclase but in both cases was less potent than ADP and did not achieve the same maximal effects.
Both actions of ADP could be inhibited by the simultaneous addition of ADP‐β‐S (50 μm).
Aggregation induced by 11α, 9α‐epoxymethano prostaglandin H2 (a stable endoperoxide analogue) was not inhibited by simultaneous addition of ADP‐β‐S (50 μm).
The behaviour of ADP‐β‐S towards human platelets was consistent with it being a partial agonist.
OPIATE‐LIKE ANALGESIC ACTIVITY IN GENERAL ANAESTHETICS
Authors: LAWRENCE D. , LIVINGSTON A. 
Published: July 2012

The interaction of naloxone with various anaesthetics was studied both in vivo and in vitro.
Naloxone (10 mg/kg) did not significantly alter the anaesthetic duration of halothane, diethylether, ketamine, pentobarbitone or Althesin.
Naloxone (10 mg/kg) reduced the analgesic activity of nitrous oxide, ketamine and morphine in the rat tail‐flick test. With the exception of pentobarbitone and Althesin, the other anaesthetic agents also induced analgesia but were not antagonized by naloxone. 4 Specific [3H]‐dihydromorphine binding was displaced by the opiates naloxone (IC50=7.6nM), methionine‐enkephalin (Met‐enkephalin, IC50=40nM) and morphine (IC50=54nM). Similarly, displacement was observed with xylazine (IC50=9μ,m), ketamine (IC50 = 130μm) and Althesin (IC50 = 150 μm); other anaesthetics agents tested were inactive in mM concentrations.
Ketamine (IC50 =200 μm) and xylazine (IC50 =9.5 μ,m) were also capable of displacing specific [3H]‐D‐Ala2‐enkephalin (D‐Leu) binding, as were morphine (IC50 = 95 nM) and Met‐enkephalin (IC50 = 40nM).
On the stimulated guinea‐pig ileum, Met‐enkephalin and morphine inhibited the contractions, the IC50 values were 30 nM and 50 nM respectively. The anaesthetics ketamine (IC50 = 10μm) and Althesin (IC50 = 8μ,m) were active. Xylazine (IC50 = 12nM) exhibited considerable potency in inhibiting the contractions on this preparation. Naloxone 0.5 μ,M produced a 1000 fold shift in the opiate dose‐response curve but the anaesthetic responses showed only slight sensitivity to antagonism by naloxone.
The activity of Althesin was found to be due to the vehicle in which this anaesthetic is solubilised.
Whilst several anaesthetic agents showed analgesic activity, specific dihydromorphine binding displacement or guinea pig ileum inhibiting activity, these effects showed variable sensitivity to naloxone.