bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF ANTIDEPRESSANT DRUGS ON NORADRENALINE ACCUMULATION AND CONTRACTILE RESPONSES IN THE RAT ANOCOCCYGEUS MUSCLE
Authors: DOGGRELL S.A. , WOODRUFF G.N. 
Published: July 2012

The effect of a series of antidepressant drugs on noradrenaline accumulation was studied in the isolated anococcygeus muscle of the rat.The most potent inhibitors of noradrenaline accumulation were nortriptyline, desipramine and protriptyline. Opipramol, trimipramine and iprindole were active only in high concentrations.Contractions of the anococcygeus muscle produced by noradrenaline were strongly potentiated by nortriptyline, desipramine and protriptyline. Other uptake inhibitors were less active in potentiating the noradrenaline response.Nortriptyline, in concentrations that potentiated the action of noradrenaline, reduced or abolished the response to tyramine.
CORONARY REACTIONS TO CARDIAC HYPERACTIVITY AND TO HYPOXIA IN ISOLATED PERFUSED HEART OF RAT
Authors: SEN A.K. , SUNAHARA F.A. , TALESNIK J. , ENDRENYI L. 
Published: July 2012

Continuous recording of cardiac force of contraction, heart rate and coronary flow from isolated perfused hearts of rats was used to study coronary reactions: (a) to cardiostimulation with noradrenaline, CaCl2, or electrically induced tachycardia; (b) to short duration stoppage of coronary inflow (hypoxia).
The heart rate was controlled by electrical pacing. Coronary vasodilatation resulted from cardiostimulation or hypoxia. This coronary response was greater at higher heart rates.
In parallel experiments administration of noradrenaline to hearts paced at different frequencies resulted in a rate‐dependent elevation of adenosine‐3′,5′‐cyclic monophosphate (cyclic AMP).
Duration of hypoxia leading to different degrees of reactive hyperaemia did not change the cardiac cyclic AMP levels.
Coronary vasodilatation due to increased cardiac metabolism produced by noradrenaline, Ca2+ or tachycardia was enhanced by the phosphodiesterase inhibitors diazoxide and papaverine while it was inhibited during the administration of prostaglandin E2.
Reactive hyperaemia was unaffected by diazoxide, papaverine or prostaglandin E2.
Catecholamine depletion by reserpine did not influence metabolic coronary dilatation nor the reactive hyperaemic responses.
We postulate that there are at least two types of coronary reactions: one in response to hypoxia, ‘reactive hyperaemia’, and another resulting from cardiac hyperactivity, ‘metabolic coronary dilatation’. The latter, blocked by prostaglandin E2 and enhanced by diazoxide or papaverine, would be triggered by cyclic AMP while reactive hyperaemia would result from other mechanisms.
COMPARISON OF THE DISCRIMINATIVE STIMULUS PROPERTIES OF COCAINE AND AMPHETAMINE IN RATS
Authors: D'MELLO G.D. , STOLERMAN I.P. 
Published: July 2012

Water‐deprived rats were trained to press either the left or the right bar in a test chamber according to whether they were injected with a central nervous system stimulant or 0.9% w/v NaCl solution (saline). Correct responses were reinforced with water.
Different groups of rats learned to discriminate amphetamine or cocaine from saline. Dose‐response curves and ED50 values were then determined in brief test sessions when no responses were reinforced.
In a crossover study, cocaine was tested in the rats trained to discriminate amphetamine from saline, and vice versa. The two drugs were largely interchangeable, but the ED50 values were increased, indicating a possible, subtle difference in their discriminative stimulus properties.
The results indicate the importance of complete crossover designs in combination with dose‐response determinations when attempting to classify drugs according to their discriminable properties.
EVIDENCE FOR TWO DIFFERENT Na+‐DEPENDENT [3H]‐OUABAIN BINDING SITES OF A Na+‐K+‐ATPASE OF GUINEA‐PIG HEARTS
Authors: FRICKE U. , KLAUS W. 
Published: July 2012

The influence of various Na+ concentrations on [3H]‐ouabain binding was studied in experiments on a microsomal Na+‐K+‐adenosine triphosphatase (ATPase) from guinea‐pig hearts.
The ATP‐independent cardiac glycoside binding was not influenced by increasing Na+ concentrations. However, a good correlation was found between the ATP‐dependent [3H]‐ouabain binding and Na+ concentration.
A more detailed analysis of these results according to Hofstee (1952) revealed two distinct processes involved in this interaction: one ouabain binding process was activated at rather low Na+ concentrations, (K0.5 = 4.5 mM); this type of [3H]‐ouabain binding was strongly correlated to the Na+ concentration necessary for half maximum phosphorylation (K0.5 = 1 mM). The other ouabain binding process was predominant at high Na+ concentrations (K0.5 = 69 mM).
On the basis of the commonly accepted ATPase reaction cycle a model for the interaction of cardiac glycosides with the Na+‐K+‐ATPase is proposed, assuming two different binding sites for cardiac glycosides (E2‐P and E1‐P) and involving a translocation of these drugs from an outer to an inner compartment of the cell membrane.
INTERDEPENDENCE OF ION TRANSPORT AND THE ACTION OF OUABAIN IN HEART MUSCLE
Authors: BENTFELD M. , LÜLLMANN H. , PETERS T. , PROPPE D. 
Published: July 2012

The influence of ouabain (0.4 μM) on contractile force and cellular Na and K concentrations was investigated in isolated left atria of the guinea‐pig at rest and at different beat frequencies. Simultaneously the binding of ouabain to the tissue was determined.
Strict dependence of rates of onset of positive iontropic action and of binding of ouabain on beat frequency are limited to conditions where no alterations of cellular Na and K concentrations occur. A correlation was observed between sodium flux per unit time and the development of positive inotropism and binding to the receptors of ouabain.
Ouabain exerts its positive inotropic effect without affecting the intracellular Na and K concentrations in spite of the fact that under these conditions even the majority of binding sites, i.e. Na‐K‐adenosine triphosphatases (Na‐K‐ATPases), are occupied by the drug. The positive inotropic effect may be explained by a ouabain‐induced conformational alteration of the Na‐K‐ATPase which leads to structural alterations of the plasmalemma connected with an increased availability of coupling calcium.
Increasing the frequency of stimulation over a critical value, which appears to be determined by an overloading of the Na pump, induces a decrease in contractile force, cellular accumulation of Na and loss of K, and eventually contracture.
The rate of binding of ouabain appears to depend on the actual concentration of particular conformations of the Na‐K‐ATPase with high affinity for ouabain. These conformations transiently occur during a pumping cycle and their concentration may therefore be dependent on the frequency of cycling which in turn is determined by the frequency of contraction.
Ouabain can easily be washed out from the tissue irrespective of the condition of the muscle. If, however, the intracellular Na and K homeostasis is impaired, the inhibition of the pump persists even if ouabain is released from the binding sites upon wash‐out. It is suggested that the inhibition of the pump is maintained by an increased intracellular Ca ion concentration and a depletion of ATP.
A kinetic model is proposed for the interaction between cardiac glycosides and the Na‐K‐ATPase in intact heart muscle cells.
SUPPRESSION OF TRANSMISSION OF NOCICEPTIVE IMPULSES BY MORPHINE: SELECTIVE EFFECTS OF MORPHINE ADMINISTERED IN THE REGION OF THE SUBSTANTIA GELATINOSA
Authors: DUGGAN A.W. , HALL J.G. , HEADLEY P.M. 
Published: July 2012

In spinal cats anaesthetized with α‐chloralose, a study was made of the effects of morphine and naloxone, administered electrophoretically from micropipettes, on the responses of dorsal horn neurones to noxious (raising of skin temperature above 45°C) and innocuous (deflection of hairs) peripheral stimuli.
Administered near cell bodies, morphine reduced the nociceptive responses of only 2 of 37 cells. Excitation occurred more commonly than depression and abnormalities in action potentials were commonly observed following ejection of morphine. None of these effects of morphine was antagonized by electrophoretically applied naloxone.
Administered in the substantia gelatinosa from one micropipette while recording responses of deeper neurones with a second micropipette, morphine reduced the nociceptive responses of 15 of 19 neurones. Firing in response to deflection of hairs was not reduced by morphine. Depression of nociceptive responses by morphine was long lasting (> 20 minutes). Naloxone ejected into the substantia gelatinosa or given intravenously in doses as low as 0.1 mg/kg antagonized the effects of morphine. The effectiveness of this dose of intravenous naloxone suggests that the concentrations of morphine in the substantia gelatinosa which reduced nociceptive responses were not unlike those present after analgesic doses of systemic morphine. Naloxone alone, and excitant and depressant amino acids ejected into the substantia gelatinosa had little effect on cell firing.
Both the selective action of morphine on nociceptive responses and the reversal of this action by intravenous naloxone suggest that the opiate receptor present in the substantia gelatinosa is relevant to analgesia produced by opiates given systemically.
INHIBITION BY A STABLE ANALOGUE OF ADENOSINE TRIPHOSPHATE OF PLATELET AGGREGATION BY ADENOSINE DIPHOSPHATE
Authors: BORN G.V.R. , FOULKS J.G. 
Published: July 2012

In citrated platelet‐rich plasma, freshly prepared from rabbit blood, the velocity of platelet aggregation was within limits proportional to the log of the concentration of added adenosine diphosphate (ADP).
Addition of either adenosine triphosphate (ATP) or its β,γ‐methylene analogue inhibited aggregation similarly except that the analogue was about half as potent as ATP. β,γ‐Methylene ATP also reversed the optical effects associated with the shape change of platelets very similarly to ATP itself.
As β,γ‐methylene ATP is not a substrate for nucleoside diphosphokinase, these observations do not support the proposition that inhibition of aggregation by added ATP is due to its utilization by the nucleoside diphosphokinase of platelets.
GUANETHIDINE‐INDUCED VASODILATATION IN THE RABBIT, MEDIATED BY ENDOGENOUS HISTAMINE
Authors: ANGUS J.A. , BOBIK A. , KORNER P.I. , STONEHAM M.T. 
Published: July 2012

The effects of guanethidine (0.5–4 mg/kg i.v.) on arterial pressure, hindlimb blood flow and hindlimb vascular resistance (HVR) were studied in unanaesthetized rabbits subjected to ‘total’ autonomic block.
Evidence that this response was mediated by histamine release was that (a) 3H‐labelled histamine levels in the hindlimb venous blood rose substantially after guanethidine; (b) infusion of exogenous histamine caused an inhibition of the guanethidine‐induced vasodilatation; and (c) competitive antagonism of the response was obtained with the H2‐antagonist burimamide.
There was good correlation between the [3H]‐histamine release and the time course of the vasodilator response. Glyceryl trinitrate infusions that lowered HVR substantially, did not cause release of histamine.
Reserpine, desipramine and indomethacin pretreatment did not alter the vasodilator response to guanethidine.
The guanethidine vasodilator response was not influenced by the H1‐antagonist mepyramine or by the other H2‐antagonists, metiamide or cimetidine. The vascular receptors stimulated by endogenous histamine may be distinctive from those stimulated by exogenous histamine, or the action of guanethidine may involve greater production of histamine at an intracellular site that is more readily reached by burimamide than by the other H2‐antagonists.
CAN SOCIAL INTERACTION BE USED TO MEASURE ANXIETY?
Authors: FILE SANDRA E. , HYDE J.R.G. 
Published: July 2012

Pairs of male rats were placed in a test box for 10 min and the time they spent in active social interaction was scored. Maximum active interaction was found when the rats were tested under low light in a box with which they were familiar. When the light level was increased or when the box was unfamiliar active social interaction decreased.
Exploration (time spent sniffing objects) decreased in the same way in relation to test conditions as did social interaction. As these decreased, defecation, and freezing increased.
Anosmic controls showed that the decrease in social interaction across test conditions could not be attributed to olfactory changes in the partner.
Chlordiazepoxide (5 mg/kg) given chronically prevented or significantly reduced the decrease in social interaction that occurred in undrugged rats as the light level or the unfamiliarity of the test box was increased. Controls showed that this effect could not be entirely attributed to chlordiazepoxide acting selectively to increase low levels of responding.
The effect of chronic chlordiazepoxide contrasts with its action when given acutely; in the latter case it has only sedative effects.
Whether this test can be used as an animal model of anxiety is discussed and this test is compared with existing tests of anxiety.
RELEASE OF MEDIATORS OF ANAPHYLAXIS: INHIBITION OF PROSTAGLANDIN SYNTHESIS AND THE MODIFICATION OF RELEASE OF SLOW REACTING SUBSTANCE OF ANAPHYLAXIS AND HISTAMINE
Authors: ENGINEER DINAZ M. , NIEDERHAUSER U. , PIPER PRISCILLA J. , SIROIS P. 
Published: July 2012

When isolated perfused lungs from sensitized guinea‐pigs were challenged with antigen, histamine, slow reacting substance of anaphylaxis (SRS‐A) and prostaglandin‐like substances were released into the effluent.
Treatment of the lungs before and during challenge with indomethacin (0.5–10 μg/ml), sodium aspirin (1–10 μg/ml), sodium meclofenamate (0.1–1 μg/ml) or ketoprofen (0.5–5 μg/ml) inhibited the release of prostaglandins while increasing the output of histamine and SRS‐A between three‐and five‐fold.
Diethylcarbamazine (0.2–1 mg/ml) reduced the release of SRS‐A and histamine but increased the amount of prostaglandin‐like substances produced.
Eicosatetraynoic acid (10 μg/ml) inhibited formation of prostaglandins but did not modify release of histamine and SRS‐A.
The results with non‐steroid anti‐inflammatory drugs and diethylcarbamazine suggest that prostaglandins, or some other product of the cyclo‐oxygenase system, depress the anaphylactic release of SRS‐A and histamine.
PHOSPHOLIPASE A2 ACTIVITY OF GUINEA‐PIG ISOLATED PERFUSED LUNGS: STIMULATION, AND INHIBITION BY ANTI‐INFLAMMATORY STEROIDS
Authors: BLACKWELL G.J. , FLOWER R.J. , NIJKAMP F.P. , VANE J.R. 
Published: July 2012

A simple double‐isotope assay for phospholipase A2 activity of perfused organs is described.
Guinea‐pig lungs perfused through the pulmonary circulation exhibit a low background enzyme activity. This activity is blocked by dexamethasone, betamethasone and hydrocortisone, mepacrine, procaine or chlorpromazine. Aspirin and indomethacin are without effect.
Mechanical trauma, antigen challenge or injections of bradykinin, rabbit aorta contracting substance‐releasing factor (RCS‐RF) or histamine increase ‘basal’ phospholipase activity. The effect of these agents, except that of bradykinin, is blocked by dexamethasone or mepacrine.
The blocking effect of steroids is cumulative and dose‐dependent. They do not work in cell‐free systems. Inhibition by mepacrine is rapid and is effective in cell‐free lung homogenates.
It is suggested that agents which liberate prostaglandin endoperoxides and thromboxane A2 from perfused lungs do so by activating phospholipase A2.
FUNCTIONAL CHANGES IN CEREBRAL 5‐HYDROXYTRYPTAMINE METABOLISM IN THE MOUSE INDUCED BY ANTICONVULSANT DRUGS
Authors: CHADWICK D. , GORROD J.W. , JENNER P. , MARSDEN C.D. , REYNOLDS E.H. 
Published: July 2012

Acute administration of clonazepam, diazepam and diphenylhydantoin to mice elevated cerebral 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA); chronic administration had less effect.
Acute administration of clonazepam and diazepam but not diphenylhydantoin raised cerebral tryptophan levels; chronic administration of clonazepam caused a smaller elevation of cerebral tryptophan but chronic administration of diazepam still caused a large rise in cerebral tryptophan.
Neither clonazepam nor diazepam caused induction of drug metabolizing enzymes on chronic administration but diphenylhydantoin had a marked effect.
These data suggest that the altered 5‐HT metabolism caused by these compounds is unrelated to a common action on tryptophan levels, and that the reduced effect of clonazepam and diazepam on chronic administration cannot be attributed to increased metabolism of these compounds.
Clonazepam induced abnormal head movements in mice in a dose‐dependent manner. Pretreatment of animals with tranylcypromine increased the intensity of movement, although pargyline was without effect. Similar effects were observed with diazepam and diphenylhydantoin, suggesting that the increase in cerebral 5‐HT caused by these compounds is of functional significance in stimulating 5‐HT receptors.
COMPARISON OF THE VASODEPRESSOR EFFECTS OF PROSTACYCLIN AND 6‐OXO‐PROSTAGLANDIN F1α WITH THOSE OF PROSTAGLANDIN E2 IN RATS AND RABBITS
Authors: ARMSTRONG J.M. , LATTIMER N. , MONCADA S. , VANE J.R. 
Published: July 2012

Vasodepressor effects of prostacyclin (5z‐5,6‐didehydro‐9‐deoxy‐6,9a‐epoxyprostaglandin F1) and its decomposition product 6‐oxo‐prostaglandin F1α (6‐oxo‐PGF1α) have been compared with those of prostaglandin E2 (PGE2) in anaesthetized rats and rabbits.
In rats intravenous prostacyclin produced hypotension and was 4–8 times more potent than PGE2 and about 128 times more potent than 6‐oxo‐PGF1α.
In rabbits also, intravenous prostacyclin (less than 2 μg/kg) produced hypotension and was twice as active as PGE2 and approximately 250 times more active than 6‐oxo‐PGF1α.
In rats and rabbits vasodepressor responses induced by prostacyclin were similar in magnitude after either intravenous or intra‐aortic administration.
Thus, in both species prostacyclin resembles PGE2 in producing vasodepression but does not lose activity on passage through the lungs. The results emphasize the need to consider prostacyclin in addition to PGE2 as a major determinant influencing blood pressure.
THE EFFECT OF LITHIUM ON THE INCREASE IN FOREBRAIN 5‐HYDROXYINDOLEACETIC ACID PRODUCED BY RAPHE STIMULATION
Authors: COLLARD K.J. 
Published: July 2012

The change in forebrain 5‐hydroxyindoleacetic acid (5‐HIAA) concentration induced by raphe stimulation has been studied in rats treated with Li+ or 0.9% w/v NaCl solution (saline) for 10 days.
Raphe stimulation increased the forebrain concentration of 5‐HIAA in both groups of animals. Chlorimipramine abolished this effect in the control group, but not in the Li+ group.
The inhibition of 5‐hydroxytryptamine (5‐HT) uptake by chlorimipramine was not affected by pretreatment with Li+ or by the addition of Li+ to synaptosomal suspensions in vitro.
It is suggested that the production of 5‐HIAA following raphe stimulation in Li+‐treated animals is derived from the metabolism of 5‐HT which remains within the intracellular environment. The consequence of this in relation to transmitter release is discussed.
THE EFFECTS OF ISOPRENALINE AND A NEW p‐SYMPATHOMIMETIC AMINE UPON SPONTANEOUS ACTIVITY, DIASTOLIC DEPOLARIZATION AND PLATEAU HEIGHT IN CARDIAC PURKINJE FIBRES
Authors: GRABOWSKI W. , LUTTGAU H. Ch. , SCHULZE J.J. 
Published: July 2012

In spontaneously active Purkinje fibres of young cows the dose‐response curves of the action of isoprenaline upon different electrophysiological parameters were measured.
The increase in slope of diastolic depolarization could roughly be described by a one‐for‐one binding curve with a half maximum effect near 10−8m and the increase in the height of the plateau level by a two‐for‐one binding curve with a half maximum effect near 10−7m (—)‐isoprenaline.
These dose‐response curves were similar to those of two parameters measured under voltage clamp conditions by other authors. The increase in slope of diastolic depolarization behaved like the shift of the activation curve for the pacemaker potassium current towards positive potentials and the growth in plateau height like the increase in the slow inward current mainly carried by Ca ions. From this conformity we propose that the parameters evaluated by us from action potential records could be used for a qualitative analysis of the action of catecholamines on pacemaker potassium current and Ca influx.
The effects of the isomers of a new drug, 1‐isopropylamino‐3(4′hydroxyphenoxy)‐propan‐2‐ol (IHP), were evaluated in the same way as those of isoprenaline. The (—)‐isomer was at optimal concentrations (10−5m) nearly half as effective as isoprenaline in increasing frequency and slope of diastolic depolarization but caused no increase in plateau height. An identical relationship, but at 5 to 10 times higher concentrations, was obtained with the (+)‐isomer.
When 10−4m(—)‐IHP was added to a preparation equilibrated with a maximum dose of (‐)‐iso‐prenaline (10−6m), frequency and plateau height declined. This result together with the observation that the effects of IHP could be blocked by the specific β‐antagonist propranolol, revealed the jff‐agonistic nature of the new drug. Its inefficiency in increasing the plateau height and thus the slow (Ca) inward current was explained by its relatively low potency and intrinsic activity.
THE EFFECT OF ERGOTAMINE ON TISSUE BLOOD FLOW AND THE ARTERIOVENOUS SHUNTING OF RADIOACTIVE MICROSPHERES IN THE HEAD
Authors: JOHNSTON BARBARA M. , SAXENA P.R. 
Published: July 2012

The radioactive microsphere method was used to study the effects of ergotamine (5, 10 and 20 μg/kg, i.v.) on systemic and regional haemodynamic variables in chloralose‐urethane anaesthetized cats. The influence of the drug was also studied on the number of 15 um microspheres escaping entrapment in the head to emerge in the left external jugular vein.
Ergotamine decreased the heart rate and cardiac output. Since arterial blood pressure remained unchanged, calculated total peripheral resistance increased.
The regional distribution of cardiac output obtained with 15 um microspheres agreed well with previous studies in cats where 25 um spheres were used. The most pronounced difference was that in the present investigation more microspheres, apparently escaping through arteriovenous anastomoses (AVAs), were detected in the lungs than when larger spheres had been used.
Coronary blood flow decreased, while uterine blood flow was increased by the drug. The microsphere content of the lungs, which receive the spheres not only via bronchial arteries but also via AVAs, was greatly reduced by all doses of ergotamine. Ergotamine did not influence tissue blood flow to other major organs such as the brain, kidneys, skin, liver, skeletal muscle or the gastrointestinal tract.
In the 16 experiments, 0.46 ± 0.05 (s.e. mean) % of the total microspheres injected (equivalent to 11.7 ± 1.4% of microspheres detected in the left‐side of the head) appeared within 2min of microsphere injection into the left external jugular vein. The highest dose of ergotamine significantly reduced the shunting of the microspheres in the head.
Since 15 um microspheres are only likely to reach the lungs by passing into the venous circulation through large glomus‐type AVAs, we conclude that ergotamine reduces the fraction of microspheres appearing in the lungs by causing strong vasoconstriction in the AVAs in the head.
In conformity with the closure of head AVAs is the finding that ergotamine reduced the jugular venous Po2 and 02 saturation thereby increasing the A‐V 02 saturation difference.
It is quite possible that decreased A‐V shunting may be the prominent mechanism of the antimigraine action of the drug, since sudden opening of AVA's has been implicated in the pathophysiology of migraine‐syndrome.