bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPASMOGENIC AND POTENTIATING ACTIONS OF SOME AMINO ACIDS ON THE GUINEA‐PIG MYOMETRIUM
Authors: BEDWANI J.R. , ISHIZAWA M. , PICKLES V.R. , SUWANKRUGHASN SURANG 
Published: July 2012

Thirty‐three amino acids were applied separately in concentrations of 2 to 10 mM to guinea‐pig uterine horns in vitro at pH 7.4. About half the acids regularly produced contractions.
Glycine and the straight‐chain L‐α‐amino acids up to norleucine were active (longer ones not tested); D‐isomers were less potent or inactive in these concentrations. The ω‐amino acids γ‐aminobutyric acid (GABA) and δ‐aminovaleric, and the α,ω‐diamino acids L‐α, β‐diaminopropionic and L‐α,γ‐diaminobutyric were active, whereas others of similar chain‐length such as β‐alanine and lysine were not. The diacidic acids, glutamic and homocysteic, were more active than the amido‐amino acids, glutamine and asparagine. Histidine and phenylalanine showed little or no activity.
The use of appropriate blocking agents indicated that the responses to representative acids were not mediated by histamine, 5‐hydroxytryptamine, acetylcholine, noradrenaline or by prostaglandins. Attempts to block the actions of glycine and GABA with strychnine, thebaine, picrotoxin, bicuculline or tetramethylenedisulphotetramine (TETS) were unsuccessful.
When some of the acids that were spasmogenic at 2 to 10 mM were applied at sub‐spasmogenic doses, they transiently potentiated other spasmogens such as oxytocin or acetylcholine. This effect was also shown by a mixture of amino acids at approximately the normal plasma concentrations.
There is some similarity between the spasmogenic activities of different amino acids and their known abilities to depolarize neurones.
THE INHIBITION OF HISTAMINE RELEASE FROM RAT PERITONEAL MAST CELLS BY NON‐STEROID ANTI‐INFLAMMATORY DRUGS AND ITS REVERSAL BY CALCIUM
Authors: LEWIS G.P. , WHITTLE B.J.R. 
Published: July 2012

The non‐steroid anti‐inflammatory drugs, indomethacin, flufenamate and meclofenamate, inhibited the release of histamine from rat peritoneal mast cells induced by pharmacological or immunological challenge in vitro.
Anti‐inflammatory steroids had little effect on histamine release from the mast cells.
Th inhibition of histamine release by the aspirin‐like drugs was not prevented by incubation with glucose, unlike the inhibition of 2,4,dinitrophenol or antimycin‐A. This suggests that the non‐steroid anti‐inflammatory compounds do not act by preventing the energy production from oxidative metabolism, required for histamine release.
The inhibition of the calcium ionophore A23187‐induced histamine release by the aspirin‐like drugs was reversed by an increase in the calcium concentration of the incubation medium.
The results suggest that the non‐steroid anti‐inflammatory compounds inhibit histamine release by actions on calcium influx into the mast cell, or on calcium mobilization or utilization within the mast cell.
THE EFFECTS OF SODIUM CROMOGLYCATE ON HISTAMINE AEROSOL‐INDUCED REFLEX BRONCHOCONSTRICTION IN THE ANAESTHETIZED DOG
Authors: JACKSON D.M. , RICHARDS I.M. 
Published: July 2012

The effects have been studied of sodium cromoglycate (SCG), given by aerosol or intravenously, on reflex bronchoconstriction induced by histamine aerosol in the anaesthetized dog.
Four breaths of an aerosol generated from a 2% solution of SCG significantly inhibited the vagally mediated increase in total lung resistance (RL) produced by histamine.
SCG given intravenously as bolus injections (5–500 μg/kg) produced a dose‐dependent reversal of a sustained reflex bronchoconstriction induced by histamine aerosol. Propranolol (500 μg/kg) did not prevent this reversal.
SCG did not inhibit the increase in RL produced by supramaximal electrical stimulation of a vagus nerve.
The possibility is discussed that SCG may reduce the activity of lung irritant receptors in the anaesthetized dog.
POSSIBLE MECHANISM OF ADVERSE REACTION FOLLOWING LEVODOPA PLUS BENSERAZIDE TREATMENT
Authors: MESSIHA F.S. 
Published: July 2012

Rats treated for seven days with seryl‐trihydroxybenzylhydrazine (benserazide), an inhibitor of peripheral aromatic l‐amino acid decarboxylase (500 mg/kg, daily, i.p.) alone or in combination with l‐DOPA methylester (500 mg/kg, daily, i.p.) for seven days showed a moderate but significant decrease of liver aldehyde dehydrogenase (ALDH), without accompanying change in alcohol dehydrogenase (ADH) activity, compared with saline‐treated controls.
Administration of l‐DOPA methylester (500 mg/kg, daily, i.p.) alone for seven days had little effect on liver ADH or ALDH.
The combined treatment might be conducive to the in vivo formation of l‐DOPA‐derived tetrahydroisoquinoline derivatives which might be implicated in l‐DOPA produced adverse effects.
METABOLIC BASIS FOR THE SUPRA‐ADDITIVE EFFECT OF THE ETHANOL‐DIAZEPAM COMBINATION IN MICE
Authors: PAUL C.J. , WHITEHOUSE L.W. 
Published: July 2012

The comination of ethanol and diazepam elicits additive or supra‐additive pharmacological effects in animals and humans. Since the mouse appeared to be a reasonably good animal model for man, this species was examined to determine if a biochemical basis for these effects could be established.
The effect of ethanol (3 g/kg, orally), administered 0.5 h before [14C]‐diazepam (5 mg/kg, orally), on the pharmacokinetics of diazepam in male Swiss Webster mice was examined.
At 4, 6, 8 and 12 h after dosing, blood levels of 14C were higher in ethanol pretreated mice than in vehicle pretreated controls. A tissue distribution study indicated that ethanol had similar effects on levels of 14C in most tissues at 2, 6 and 12 hours.
Both pretreated and control mice eliminated approximately 25% of the dose of isotope in the urine and 50% in the faeces by 48 hours.
Biliary excretion was the major route of clearance in mice in which the bile ducts had been cannulated and ethanol reduced excretion at all time periods examined up to 12 hours.
Oxazepam (the glucuronide in bile) and desmethyl diazepam were the major metabolites identified in bile, plasma and brain. Ethanol reduced oxazepam levels but increased desmethyl diazepam levels, suggesting that 3‐hydroxylation of desmethyl diazepam was inhibited by ethanol.
The accumulation of the pharmacologically active desmethyl diazepam in the brains of ethanol pretreated mice offers an explanation for the supra‐additive effect of the ethanol‐diazepam combination on motor coordination.
RESPONSES OF THE CARDIOVASCULAR SYSTEM OF THE RAT TO α‐ AND β‐ADRENOCEPTOR AGONISTS
Authors: IMMS F.J. , NEAME R.L.B. , POWIS D.A. 
Published: July 2012

The effects of intravenously infused phenylephrine and isoprenaline upon the cardiovascular system of the rat anaesthetized with pentobarbitone, have been investigated.
Phenylephrine produces a dose‐dependent rise in mean arterial blood pressure (MABP) that is due mainly to an increase in total peripheral vascular resistance (TPR), though at all doses tested cardiac output was invariably raised.
The increase in cardiac output was due in each instance to an increase in stroke volume, heart rate being unchanged. This increase in cardiac output is probably brought about by effects of phenylephrine on the capacitance vessels rather than by an effect on the heart.
Evidence is presented to show that the effects of phenylephrine are mediated largely by α‐adrenoceptors, but that β‐adrenoceptors which affect TPR are also stimulated by the amine.
Isoprenaline produces a dose‐dependent fall in MABP that is due entirely to a fall in TPR since the cardiac output increases.
Unlike phenylephrine, the increase in cardiac output obtained with isoprenaline was achieved by an increase in heart rate while stroke volume remained close to control values. It is contended that the augmented venous return required for the elevated cardiac output results in this case mainly from the isoprenaline‐induced fall in TPR which enhances transfer of blood from arteries to the veins.
Evidence is presented to show that the effects of isoprenaline are mediated mainly by β‐adrenoceptors.
Under the present experimental conditions the adrenoceptor‐mediated cardiovascular changes are little modified reflexly by the arterial baroreceptors.
THE NATURE OF POTASSIUM CHLORIDE‐INDUCED RELAXATIONS OF THE RAT ANOCOCCYGEUS MUSCLE
Authors: GIBSON A. , JAMES T.A. 
Published: July 2012

The nature of KCl‐induced relaxations of the rat anococcygeus muscle was investigated.
The relaxations were mimicked by other K+ salts, but not by NaCl.
The muscle was more susceptible to the relaxant effects of KCl than the contractile effects.
Addition of ouabain (100 μm) had no effect on the relaxations.
The relaxations were abolished by tetrodotoxin (5 μg/ml), procaine (500 μm), and by section of the inhibitory nerves.
The results suggest that KCl‐induced relaxations are due to stimulation of the inhibitory nerves by K+.
COMPARATIVE EFFECTS OF GLYCERYL TRINITRATE ON VENOUS AND ARTERIAL SMOOTH MUSCLE in vitro; RELEVANCE TO ANTIANGINAL ACTIVITY
Authors: MACKENZIE J.E. , PARRATT J.R. 
Published: July 2012

A quantitative in vitro study has been made of the actions of glyceryl trinitrate and sodium nitrite on vascular smooth muscle (dog femoral artery and saphenous vein; rat portal vein); these have been compared with the actions of papaverine, isoprenaline, salbutamol, pentaerythritol tetranitrate and trimetazidine.
Glyceryl trinitrate was more active on the saphenous vein than on the femoral artery in inhibiting noradrenaline and potassium‐induced tone.
Unlike glyceryl trinitrate, sodium nitrite and isoprenaline, papaverine and diazoxide inhibited noradrenaline‐induced contractions of venous and arterial smooth muscle to the same extent.
The selective dilator effects of glyceryl trinitrate on venous smooth muscle may explain its action in alleviating the pain of angina pectoris. It is suggested that the use of these three vascular smooth muscle preparations (arterial, and veins with and without spontaneous myogenic activity) is a useful initial screening procedure for prospective antianginal drugs acting by venodilatation.
TIME COURSES OF THE ANTI‐ANAPHYLACTIC AND ANTI‐INFLAMMATORY EFFECTS OF DEXAMETHASONE IN THE RAT AND MOUSE
Authors: CHURCH M.K. , MILLER P. 
Published: July 2012

The time course of the activity of dexamethasone has been studied in a variety of anaphylactic and inflammatory reactions in the rat and the mouse.
The times of peak activity of dexamethasone, expressed as time between oral dosage and induction of response, and the approximate ED50 values (mg/kg) found were: anaphylactic bronchoconstriction in rats, 12–24 h, ED50 1.8; passive cutaneous anaphylaxis in rats, 6 h, ED50 0.04; cutaneous reactions to histamine in rats, 4 h, ED50 0.01; carrageenin‐induced paw oedema in rats, 4 h, ED50 0.03; pinnal anaphylaxis in mice, 6 h, ED50 0.82; histamine‐induced pinnal reactions in mice, 6 h, ED50 0.05.
In rats, the characteristics of the inhibitory effects of dexamethasone indicate a differential activity against anaphylactic and inflammatory reactions and between different types of inflammatory reactions. Possible reasons for these differences are discussed.
In mice there was little difference between the inhibition by dexamethasone of cutaneous allergic and histamine‐induced reactions.
Pinnal anaphylaxis in mice was potentiated by dexamethasone given 1–2 h before challenge.
DIFFERENTIAL DEPLETION OF CYTOPLASMIC HIGH AFFINITY OESTROGEN RECEPTORS AFTER THE in vivo ADMINISTRATION OF THE ANTIOESTROGENS, CLOMIPHENE, MER‐25 AND TAMOXIFEN
Authors: KURL R.N. , MORRIS I.D. 
Published: July 2012

The in vivo actions of the oestrogen antagonists clomiphene, MER‐25 and tamoxifen upon the cytosol oestrogen receptors prepared from amygdala, hypothalamus, pituitary and uterus of rats were studied 24 h after drug administration.
There was a dose‐related depletion of cytosol oestrogen receptors. However, the uterine and pituitary receptors were consistently affected at a lower dose than were those from the brain.
The ratios of the combined central ED50 to the combined peripheral ED50 were clomiphene 169 < MER‐25 19.2 > tamoxifen 2.13.
The receptor changes were not related to biological activity monitored by serum luteinizing hormone levels and uterotrophic response.
The possible role of these drug effects in the induction of ovulation and future developments are discussed.
INVESTIGATION OF THE ROLE OF HISTAMINE IN ANTIGEN‐INDUCED BRONCHOCONSTRICTION IN THE ASCARIS‐HYPERSENSITIVE DOG
Authors: KRELL ROBERT D. 
Published: July 2012

Aerosol administration of ascaris antigen to the airways of ascaris‐hypersensitive dogs provoked increases in pulmonary resistance (Rp) and decreases in dynamic lung compliance (Cdyn). These changes in pulmonary mechanics were not inhibited by the histamine H1‐receptor antagonists, diphenhydramine or mepyramine.
Increases in Rp and decreases in Cdyn induced by a histamine aerosol were markedly or totally inhibited by comparable doses of these HI‐antihistamines.
Doses of antigen which produced pathophysiological pulmonary responses failed to produce a detectable histamine release from the cardiopulmonary system in vitio. Aerosol antigen provocation, equivalent to 5 to 9 times greater than that which produced substantial pathophysiological pulmonary responses, did cause histamine release in vivo.
The canine cardiopulmonary system showed only a modest ability to remove and/or degrade circulating histamine.
It is concluded that histamine may not play a major role in mediating the acute antigen‐induced bronchoconstriction in the ascaris‐hypersensitive dog.
CHARACTERIZATION OF RECEPTORS MEDIATING 5‐HYDROXYTRYPTAMINE‐ AND CATECHOLAMINE‐INDUCED PLATELET AGGREGATION, ASSESSED BY THE ACTIONS OF α‐ AND β‐BLOCKERS, BUTYROPHENONES, 5‐HT ANTAGONISTS AND CHLORPROMAZINE
Authors: BOULLIN DJ. , GLENTON PATRICIA A.M. 
Published: July 2012

Blood platelets from normal human volunteers were isolated and aggregated in vitro with 5‐hydroxytryptamine (5‐HT), noradrenaline (NA), dopamine and N‐dimethyldopamine (DMDA).
The effects of 5‐HT antagonists, α‐ and β‐adrenoceptor blocking agents, butyrophenones and chlorpromazine upon aggregation induced by the four amines were investigated.
Only the 5‐HT antagonists, chlorpromazine and spiroperidol were potent inhibitors of 5‐HT‐induced aggregation, and only phentolamine was a potent inhibitor of the catecholamine‐induced aggregation.
Evidence was obtained for two populations of receptors, one for 5‐HT and one for the three catecholamines.
THE INFLUENCE OF AN EXTRANEURONAL COMPARTMENT ON THE RELAXATION OF THE CAT NICTITATING MEMBRANE in vivo
Authors: ECCLES R. , MACLEAN A.G. 
Published: July 2012

Contractions of the cat nictitating membrane were elicited on stimulation of the internal carotid nerve, and the effects were studied of desipramine and two inhibitors of catechol‐O‐methyltransferase, U‐0521 and pyrogallol, on the subsequent relaxation of the muscle.
The relaxation of the nictitating membrane occurred in at least two phases. The late phase of relaxation was prolonged after increase in the period of nerve stimulation and the duration of this phase was further prolonged after treatment with pyrogallol.
After inhibition of neuronal uptake of noradrenaline with desipramine both the early and late phases of relaxation were increased in duration, and subsequent administration of pyrogallol or U‐0521 caused a further increase in the duration of the late phase of relaxation.
The results suggest that the late phase of relaxation of the nictitating membrane is influenced by efflux of noradrenaline from an extraneuronal pool.
CENTRAL ADRENOCEPTORS AND CHOLINOCEPTORS IN CARDIOVASCULAR CONTROL
Authors: BHARGAVA K.P. , JAIN L.P. , SAXENA A.K. , SINHA J.N. , TANGRI K.K. 
Published: July 2012

In cats anaesthetized with chloralose, adrenoceptor and cholinoceptor agonists and antagonists were localized to the posterior hypothalamus (PH), lateral medullary pressor area (LMPA) and spinal autonomic loci to delineate the role of central cholinoceptors and adrenoceptors in cardiovascular control.
All along the neuroaxis, the α‐adrenoceptors seem to subserve an inhibitory and the β‐adrenoceptors a facilitatory role in cardiovascular control. There appears to be a predominance of α‐adrenoceptors at the medullary level and β‐adrenoceptors at the hypothalamic level.
The nicotinic cholinoceptors at the hypothalamic, medullary and spinal levels were facilitatory, whereas muscarinic cholinoceptors were inhibitory for cardiovascular control. However, muscarinic receptors were undetectable at the posterior hypothalamus.
The central cardiovascular effects of nicotine are attributed to nicotinic receptor activation and release of central catecholamines.
There appears to be a relationship between central cholinergic and adrenergic mechanisms in cardiovascular control.
EFFECTS OF SPIPERONE ON SELF‐STIMULATION AND OTHER ACTIVITIES OF THE MONGOLIAN GERBIL
Authors: FRANCIS N. , MARLEY E. , STEPHENSON J. D. 
Published: July 2012

Self‐stimulation to lever pressing and capacitance probe touching was obtained in Mongolian gerbils (Meriones unguiculatus) from electrode placements within the medial forebrain bundle.
Lever pressing was more sensitive to the decremental effects of a central depressant, pentobarbitone, than capacitance probe touching, suggesting its greater responsiveness to disturbances of motor function.
Spiperone (0.005 to 0.05 mg/kg) attenuated capacitance probe touching and lever pressing equally, a finding explained by action on either reward pathways or on the ability to initiate responding.
This same dose range of spiperone (0.005 to 0.05 mg/kg) attenuated locomotor activity, whether spontaneous or evoked by non‐contingent electrical stimulation, and produced catalepsy.
The spiperone‐induced attentuation of self‐stimulation was not necessarily a result of its action on dopaminergic reward pathways since the effects could equally well be explained by a failure to initiate responding.
INHIBITION BY MORPHINE OF PROSTAGLANDIN‐STIMULATED FLUID SECRETION IN RAT JEJUNUM
Authors: COUPAR I.M. 
Published: July 2012

Anaesthetized rats (225 to 300 g) were used to study the inhibitory effect of morphine on fluid secreted by the small intestine.
Small intestinal fluid secretion was stimulated by infusion of prostaglandin E1 (PGE1) into the aortic arch, the jejunum being more sensitive than the ileum. Infusion of PGE1 2 μg/min caused maximal net fluid secretion in the jejunum but inhibited net fluid absorption in the ileum.
Morphine caused a dose‐related inhibition of maximal PGE1‐stimulated fluid secretion in the jejunum. At the higher doses of morphine used (5 to 20 mg/kg) the fluid transporting function of the jejunum was restored almost to normal net absorption.
The inhibitory effect of morphine on PGE1‐stimulated fluid secretion was antagonized by naloxone. Naloxone caused a parallel shift to the right of the dose‐response curve for morphine.
Two other narcotic analgesics were assayed relative to morphine and their descending order of potency was oxymorphone < morphine > pethidine.
It is suggested that the antisecretory effect of morphine in the small intestine may contribute to its efficacy as an anti‐diarrhoeal drug. Further studies on the rat jejunum may show it to be a useful model for predicting narcotic drug activity and as such, may give some insight into the mechanisms of action of these drugs.
PHARMACOLOGICAL AND ELECTROPHYSIOLOGICAL STUDIES OF MORPHINE AND ENKEPHALIN ON RAT SUPRASPINAL NEURONES AND CAT SPINAL NEURONES
Authors: DAVIES J. , DRAY A. 
Published: July 2012

The actions of morphine, methionine and leucine enkephalin, administered electrophoretically, were studied on supraspinal neurones in the cortex and brainstem of the rat anaesthetized with urethane and on spinal Renshaw cells and dorsal horn interneurones in the cat anaesthetized with pentobarbitone.
The majority of Renshaw cells and cortical and brainstem neurones were excited by all three compounds although some supraspinal neurones were depressed.
Naloxone reversibly antagonized both excitatory and depressant actions of morphine and enkephalin. Acetylcholine‐induced excitation but not amino acid‐induced excitation was also antagonized by naloxone.
Neither morphine nor the enkephalins had any naloxone‐reversible action on dorsal horn neurones when ejected from conventional multibarrelled electrodes. However, morphine but not enkephalin, administered into the substantia gelatinosa region of the spinal cord selectively reduced responses to noxious stimuli of neurones in deeper laminae. Naloxone administered into the same region antagonized this action of morphine.
Intravenous morphine also antagonized responses of dorsal horn neurones to noxious stimuli and subsequent intravenous naloxone reversed this effect.
It was concluded that the excitatory and inhibitory effects of morphine and enkephalin on central neurones may be mediated by actions on different opiate receptors and that depression of noxious responses of dorsal horn neurones may be relevant to the analgesic action of morphine.
TACHYPHYLAXIS TO ETHACRYNIC ACID IN THE ISOLATED ATRIUM OF GUINEA‐PIG AND ITS RELATION TO NORADRENALINE STORES
Authors: KHOYI M.A. , POUSTI A. , POWIS G. , ZARRINDAST M.R. 
Published: July 2012

The isolated electrically‐paced atrium of the guinea‐pig developed a dose‐dependent increase in the force of contraction in response to ethacrynic acid (12–100 μg/ml) which was blocked by pretreatment of the animals with reserpine but was unaffected by desipramine or colchicine added to the bathing medium.
There was a rapidly developing tachyphylaxis to repeated doses of ethacrynic acid which was not reversed by rest or incubation of the tissue with noradrenaline.
There was no cross tachyphylaxis between ethacrynic acid and tyramine, amphetamine or nicotine.
Ethacrynic acid (200 μg/ml) decreased the noradrenaline content of the atria by 32%.
It is concluded that ethacrynic acid exerts its effects indirectly through the release of endogenous noradrenaline and that the mechanism of release seems to be different from that of other known indirect sympathomimetic drugs.
RESPONSES OF RABBIT PORTAL VEIN TO HISTAMINE
Authors: COOK D.A. , MACLEOD K.M. 
Published: July 2012

Histamine produced a dose‐dependent contraction of the isolated portal vein of the rabbit. This contraction was not antagonized by atropine, methysergide, indomethacin, cocaine or 6‐hydroxydopamine, nor by pretreatment of the rabbit with reserpine.
The response to histamine was blocked by H1‐receptor antagonists only when the blocking agent was used in very high concentrations, and was not antagonized by the H2‐receptor blocking agent, metiamide. H1‐receptor antagonists did not block the effects of 5‐hydroxytryptamine.
The contractions elicited by histamine, 5‐hydroxytryptamine and noradrenaline were blocked by phentolamine.
Desensitization to high doses of 5‐hydroxytryptamine caused a concomitant depression in the response to histamine but not to noradrenaline or acetylcholine.
The results suggest that the contractions of rabbit portal vein elicited by histamine are not mediated by receptors of the H1‐ or the H2‐type, but may involve an action of histamine at a receptor which is also involved in the action of 5‐hydroxytryptamine.