bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECT OF SODIUM‐n‐DIPROPYL ACETATE ON γ‐AMINOBUTYRIC ACID‐DEPENDENT INHIBITION IN THE RAT CORTEX AND SUBSTANTIA NIGRA IN RELATION TO ITS ANTICONVULSANT ACTIVITY
Authors: KERWIN R.W. , OLPE H.‐R. , SCHMUTZ M. 
Published: July 2012

We have examined the time course of the anticonvulsant property of valproate sodium on electroshock‐induced convulsions in rats and a comparison of this has been made with the action of the drug on single unit activity in the rat brain.
Intraperitoneal valproate sodium (100 to 400 mg/kg) protected rats from electroshock‐induced convulsion. This effect was dose‐dependent, the latency of the effect decreasing as a function of dose from 5 to 2 min.
The time course of this anticonvulsant property was paralleled by a pronounced inhibition of the spontaneous firing rate of cortical and nigral neurones, following intraperitoneal administration of valproate sodium (100 to 400 mg/kg).
The inhibitory action of microiontophoretically applied γ‐aminobutyric acid (GABA) and muscimol on the firing rate of cortical neurones was potentiated within 1 to 3 min of microiontophoretic application of valproate sodium. In contrast, the inhibitory action of glycine on cortical neurones was unaffected during the microiontophoretic application of valproate sodium.
Microiontophoretically applied valproate sodium also potentiated inhibitory responses to GABA in rats which had received 100 mg/kg of a GABA‐transaminase inhibitor, gabaculine, i.p. 16 h previously.
The duration of trans‐synaptic inhibitory responses recorded in the substantia nigra and cortex following submaximal electrical stimulation of the striatum and cortex respectively was, in general, unaffected by either intraperitoneal or local application of valproate sodium.
These observations are discussed in terms of the mechanisms underlying the rapid onset of the anticonvulsant properties of valproate sodium.
AN INCREASED CALCIUM SENSITIVITY OF MESENTERIC RESISTANCE VESSELS IN YOUNG AND ADULT SPONTANEOUSLY HYPERTENSIVE RATS
Authors: MULVANY M.J. , NYBORG N. 
Published: July 2012

We have measured the calcium sensitivity in response to noradrenaline stimulation and potassium depolarization of isolated segments of 100 to 200 μm mesenteric resistance vessels from spontaneously hypertensive (SHR) and control Wistar‐Kyoto (WKY) rats. The rats were either young (4 wk) or adult (4 months), that is of ages before or after the SHRs had developed elevated blood pressure. Experiments were performed under conditions in which the effect of noradrenaline uptake by, and the potassium‐induced noradrenaline release from, the nerve terminals in the vessel walls was eliminated.
The response of the SHR and WKY vessels to noradrenaline under conditions where only the extracellular calcium appeared to have been removed was similar. When subsequently stimulated maximally by noradrenaline, the calcium‐sensitivity of the SHR vessels (Ca‐ED50 ≃ 0.1 mm) was greater than that of the WKY vessels (Ca‐ED50 ≃ 0.2 mm). When depolarized by potassium, all vessels were less sensitive to calcium and there was little difference in the calcium sensitivity of SHR and WKY vessels in either age group (Ca‐ED50 ≃ 0.8 mm).
The results suggest that whereas the potassium (potential)‐dependent calcium permeability of the SHR smooth muscle cell membrane is normal, the noradrenaline‐induced calcium permeability is abnormally high. The presence of this abnormality in the vessels from the young SHRs suggests that it may be a factor involved in the aetiology of hypertension in the SHR.
CHARACTERIZATION OF THE RECEPTOR MEDIATING THE ANTI‐ANAPHYLACTIC EFFECTS OF β‐ADRENOCEPTOR AGONISTS IN HUMAN LUNG TISSUE in vitro
Authors: BUTCHERS P.R. , SKIDMORE I.F. , VARDEY C.J. , WHEELDON A. 
Published: July 2012

The rank order of potency of six β‐adrenoceptor agonists as inhibitors of the anaphylactic release of histamine from fragments of passively sensitized human lung in vitro was (‐)‐isoprenaline > (‐)‐adrenaline > (±)‐salbutamol > (‐)‐noradrenaline > R0363 > H133/22.
The β‐adrenoceptor antagonists, propranolol, atenolol and H35/25, blocked the response to both (‐)‐isoprenaline and (±)‐salbutamol competively. Each antagonist gave similar pA2 values with both agonists. pA2 values were consistenly at the high end of the range expected for interaction at a β2‐adrenoceptor.
Practolol did not antagonize isoprenaline in a competitive manner but was a competitive antagonist of salbutamol with a pA2 at the high end of the range expected for interaction at a β2‐adrenoceptor.
Data obtained with agonists are consistent with the receptor being of the β2‐subtype. Data obtained with antagonists indicate a consistently higher affinity for the receptor than observed for the β2‐subtype in other tissues but do not suggest a novel β‐adrenoceptor subtype on the mast cell of the human lung.
SOME DIRECT AND REFLEX CARDIOVASCULAR ACTIONS OF PROSTACYCLIN (PGI2) AND PROSTAGLANDIN E2 IN ANAESTHETIZED DOGS
Authors: CHAPPLE D.J. , DUSTING G.J. , HUGHES R. , VANE J.R. 
Published: July 2012

The aim of the study was to determine the mechanism of the hypotension and bradycardia produced by prostacyclin (PGI2).
Haemodynamic studies were carried out in nineteen open‐chest beagle dogs anaesthetized with chloralose. PGI2 was infused intravenously or into the left atrium.
Infusions of PGI2 either intravenously or into the left atrium equally reduced arterial pressure and total peripheral resistance but bradycardia was greater after infusion into the left atrium.
Comparison of effects of PGI2 with those of prostaglandin E2 (PGE2) showed that although left atrial infusions both reduced aortic pressure and total peripheral resistance, PGE2 always increased heart rate, cardiac output and maximum acceleration.
Similar effects were observed with sodium nitroprusside except that it always caused tachycardia and reduced stroke volume.
Atropine (0.05 or 1 mg/kg i.v.) reduced or reversed the bradycardia induced by PGI2 but its hypotensive effects were reduced only after 1 mg/kg atropine. After vagotomy changes in cardiac output, stroke volume and maximum acceleration were increased, the hypotensive effects of PGI2 were reduced and the bradycardia was reversed; effects induced by PGE2 were not significantly altered.
The hypotension induced by prostacyclin is due to two components, a direct relaxation of vascular smooth muscle and a reflex, non‐cholinergic vasodilatation. The bradycardia is reflex in nature and is partially mediated by the vagus pathway.
BLOCKADE OF ADRENALINE‐INDUCED HYPERGLYCAEMIA IN THE ANAESTHETIZED CAT BY CONTINUOUS INFUSION OF PHENTOLAMINE AND PROPRANOLOL
Authors: AL‐JIBOURI LAYLA M. , FURMAN B.L. , PARRATT J.R. 
Published: July 2012

The effects of adrenoceptor blocking drugs on the metabolic responses to adrenaline infusion (1 μg kg−1 min−1) have been studied in the anaesthetized, fasted cat.
Propranolol, in doses (0.25 or 1 mg/kg) which prevented completely adrenaline‐induced tachycardia, reduced but did not abolish adrenaline‐induced hyperglycaemia.
Phentolamine infusion, at a rate (15 μg kg−1 min−1 after a priming dose of 2.5 mg/kg) which reversed the pressor effect of adrenaline, reduced but did not abolish adrenaline‐induced hyperglycaemia.
The continuous infusion of a combination of phentolamine (15 μg kg−1 min−1 after a priming dose of 2.5 mg/kg) and propranolol (5 μg kg−1 min−1 after a priming dose of 0.25 mg/kg) prevented completely the hyperglycaemia response to adrenaline infusion over a 6 h period.
The increase in blood lactate concentration produced by adrenaline was prevented completely by the combined infusion of propranolol and phentolamine but was not modified by phentolamine alone.
ATROPINE INHIBITS THROMBOXANE A2 GENERATION IN ISOLATED LUNGS OF THE GUINEA‐PIG
Authors: BERTI F. , FOLCO G.C. , GIACHETTI A. , MALANDRINO S. , OMINI G. , VIGANÒ T. 
Published: July 2012

Histamine (0.5 to 5 μg) and slow reacting substance of anaphylaxis (SRS‐A, 0.05 to 0.3 u), injected in the isolated, perfused lungs of normal and ovalbumin‐sensitized guinea‐pigs, promote formation and release of thromboxane A2(TXA2) and other arachidonate metabolites, the effect being more pronounced in sensitized lungs.
Carbachol injected (1 to 10 μg) or perfused (1 μg ml−1 min−1) through normal or sensitized lungs does not elicit formation of TXA2 and prostaglandins. Furthermore the increased generation of arachidonate metabolites due to histamine is not altered by carbachol.
Atropine and ipratropium bromide (1 μg ml−1 min−1) reduce significantly the increased rate of production of TXA2 caused by histamine and SRS‐A both in normal and sensitized lungs, whereas hexamethonium (10 to 25 μg ml−1 min−1) is ineffective.
The mechanism of action of atropine in inhibiting the increased generation of TXA2 is clearly not related to its antimuscarinic or antihistaminic properties. The drug might act at the early events, involved in the activation of arachidonic acid metabolism. The results suggest new sites of action for atropine which, besides the control of the vagal bronchomotor tone, interferes directly with the primary mediators of anaphylaxis.
RESPONSIVENESS TO VASOACTIVE AGENTS OF CEREBRAL AND MESENTERIC ARTERIES ISOLATED FROM CONTROL AND RESERPINE‐TREATED DOGS
Authors: HAYASHI SHIGEHIRO , MIYAZAKI MIZUO , TODA NOBORU 
Published: July 2012

Pretreatment of dogs for 20 to 24 h before the start of experiments with reserpine (0.5 mg/kg) depleted noradrenaline from cerebral and mesenteric arteries, the diminution being greater in the latter arteries.
Contractile responses of helically‐cut strips of cerebral and mesenteric arteries to noradrenaline were unaffected by pretreatment with reserpine. Tyramine‐induced contractions of mesenteric arteries were markedly attenuated by reserpine‐pretreatment, whereas the contraction of cerebral arteries was not influenced. The contractile response of mesenteric arteries to transmural nerve stimulation or nicotine was abolished by reserpine‐pretreatment, but the relaxation induced by nicotine of cerebral arteries contracted with prostaglandin F2α was not affected Pretreatment with reserpine attenuated the contractions of mesenteric arteries induced by angiotensin II, but did not alter the response of cerebral arteries to 5‐hydroxytryptamine.
In prostaglandin‐contracted cerebral and mesenteric arterial strips, relaxant effects of acetylcholine, isoprenaline and K+ were not significantly influenced by reserpine‐pretreatment.
It appears that tyramine and nicotine do not release noradrenaline from dog cerebral arteries in amounts sufficient to cause significant contractions. Attenuation of the response to angiotensin II by pretreatment with reserpine is not the result of depletion of noradrenaline from the mesenteric arterial wall but may be due to interference with the mechanism specific to actions of angiotensin II.
METABOLISM OF [3H]‐(±)‐ISOPRENALINE BY ISOLATED ATRIA AND CORONARY ARTERIES OF THE KITTEN
Authors: CORNISH E.J. , GOLDIE R.G. 
Published: July 2012

Isolated coronary arteries of the kitten accumulated more unchanged isoprenaline and metabolized more amine than atria following incubation for 1 to 20 min with [3H]‐(±)‐isoprenaline (25 ng/ml or 5 μg/ml).
Cortisol (10 or 80 μm), U‐0521 (120 μm) and oxytetracycline (100 μm) all reduced metabolite formation.
Cortisol inhibited ‘Iso InfluxMin’ (cellular isoprenaline accumulation plus total metabolite production). In contrast, it increased, decreased or did not alter accumulation of unmetabolized isoprenaline, depending upon the experimental conditions.
Isoprenaline accumulation was increased in atria and reduced in coronary arteries by U‐0521, while oxytetracycline reduced accumulation in coronary arteries at the high amine concentration.
It is concluded that in atria, cortisol inhibits metabolism and has differential effects on a number of extraneuronal compartments which accumulate isoprenaline. Both cortisol and U‐0521 appear to be extraneuronal uptake inhibitors and inhibitors of catechol‐O‐methyltransferase in coronary arteries. Oxytetracycline may have effects additional to inhibition of isoprenaline binding to connective tissue fibres.
COMPARATIVE STUDIES ON THE EFFECTS OF TOLMESOXIDE (Rx71107), A TOLMESOXIDE METABOLITE (Rx71112) AND NIFEDIPINE IN ISOLATED BLOOD VESSELS
Authors: MIKKELSEN ERICH , PEDERSEN OLE LEDERBALLE 
Published: July 2012

The effect was studied of tolmesoxide (Rx71107), a tolmesoxide metabolite (Rx71112) and nifedipine on active tension in human isolated crural veins and in rat thoracic aorta. The effects of tolmesoxide and nifedipine on 22Na and 45Ca net influx in noradrenaline‐induced contractions were investigated in rat thoracic aorta.
Tolmesoxide, Rx71112 and nifedipine caused a concentration‐related inhibition of noradrenaline (NA)‐ and potassium (K+)‐induced contractions in human veins. Nifedipine was by far the most potent drug in these respects. Tolmesoxide (4.7μm‐4700 μm) and Rx71112 (22 μm‐220 μm) inhibited the NA‐induced contraction more effectively than the K+‐induced concentration. The reverse was true for nifedipine (0.0023‐3 μm).
Nifedipine had a similar potency in inhibiting the NA‐induced contraction in rat aorta and human veins, whereas the inhibitory effect of tolmesoxide was more pronounced in rat aorta than in human veins.
Tolmesoxide was a weak antagonist of the contractile effects of the cumulative addition of calcium on human veins. In concentrations up to 470 μm, tolmesoxide was completely devoid of inhibitory effects on 22Na and 45Ca net influx in rat aorta. Rx71112 (220 μm) had an inhibitory effect on 22Na net influx but no significant effect on 45Ca net influx.
Nifedipine was an effective antagonist of the contractile effects of cumulative addition of calcium in human veins and had a concentration‐related inhibitory effect on both 22Na and 45Ca uptake in rat aorta.
The results indicate that tolmesoxide and Rx71112 cause dilatation of human crural veins in vitro at concentrations that do not interfere with the net transmembranal movements of Ca and are thus clearly different from the effects of nifedipine.
BTS 39 542, A DIHYDROPHTHALAZIN‐1‐YLACETIC ACID WITH HIGH EFFICACY DIURETIC ACTIVITY
Authors: COOLING M.J. , SIM M.F. 
Published: July 2012

BTS 39 542, a novel dihydrophthalazin‐1 ‐ylacetic acid, has high efficacy diuretic activity in mice, rats, rabbits and dogs. It is twice as potent as frusemide in mice and dogs, ten times as potent in rats and twenty times as potent in rabbits
BTS 39 542, like frusemide, exerts its major effects in the loop of Henle and increases renal blood flow but does not affect glomerular filtration rate in dogs
The ratio of the excretion of the major cations (sodium plus potassium) to that of the major anion (chloride) after either BTS 39 542 or frusemide varied with species. In rats and rabbits the ratio was approximately unity but in mice and dogs the ratio consistently exceeded unity
A method for evaluating diuretics based on potency and relative potassium excretion is described.
EFFECTS OF OXOLINIC ACID ON THE SLEEP‐WAKEFULNESS CYCLE OF THE RAT
Authors: D'ANGELO L. , MONTI J.M. 
Published: July 2012

A study was carried out in rats (prepared for chronic sleep recording) of the effects of oxolinic acid on the sleep‐wakefulness cycle
In addition, the actions of oxolinic acid on the sleep‐wake cycle were assessed after pretreatment with drugs interfering with central catecholamine mechanisms or facilitating central γ‐aminobutyric acid (GABA) activity
Oxolinic acid (8–32 mg/kg) induced a significant and dose‐related increase of waking EEG, while slow wave and REM sleep were decreased
The effects of oxolinic acid on waking, slow wave and REM sleep were antagonized by α‐methyl‐p‐tyrosine (50–100 mg/kg) which interferes with the synthesis of catecholamines
FLA‐63 (25 mg/kg) which is a specific inhibitor of noradrenaline synthesis, was effective in blocking oxolinic acid‐related increase of waking and decrease of slow wave sleep
Haloperidol (0.4‐0.6 mg/kg) which blocks central dopamine and noradrenaline receptors, reversed oxolinic acid‐induced actions on waking and slow wave sleep. Spiroperidol (2–4 mg/kg) which interferes with dopamine and 5‐hydroxytryptamine mechanisms, only antagonized the effect of oxolinic acid on light slow wave sleep. REM sleep was further decreased by both neuroleptic agents
γ‐Hydroxybutyrate (25–50 mg/kg), which acts as a GABA agonist and amino‐oxyacetic acid (20 mg/kg), which considerably increases central GABA levels, were ineffective in blocking oxolinic acid‐related disruption of the sleep‐wake cycle
Our results suggest that the catecholamines are involved in the arousing effect of oxolinic acid.
DISSIMILAR EFFECTS ON BODY TEMPERATURE IN THE CAT PRODUCED BY GUANOSINE 3‘, 5’‐MONOPHOSPHATE, ACETYLCHOLINE AND BACTERIAL ENDOTOXIN
Authors: DASCOMBE M.J. , MILTON A.S. 
Published: July 2012

Guanosine 3′, 5′‐monophosphate (cyclic GMP) and N2‐2′‐O‐dibutyryl guanosine 3′, 5′‐monophosphate (db cyclic GMP) have been injected into the third cerebral ventricle (i.c.v.) of the unanaesthetized cat and the effects on rectal temperature and on behavioural and autonomic activities observed and compared with those of acetylcholine and physostigmine
Acetylcholine (100 nmol) and physostigmine (100 nmol) injected together i.c.v. produced a rise in body temperature in cats at an environmental temperature of 20–24°C, which was abolished by pretreatment i.c.v. with atropine (200 nmol)
Cyclic GMP and db cyclic GMP (10–1250 nmol) had no effect on body temperature in cats at an environmental temperature of 20–24°C but produced hypothermia (1250 nmol) in cats at an environmental temperature of 9–11°C
The O‐somatic antigen of Shigella dysenteriae (20 μg/kg i.v.) produced fever in cats which was not potentiated by caffeine (25 mg/kg i.p.). Levels of endogenous cyclic GMP in c.s.f. taken from the cisterna magna during fever induced by bacterial endotoxin in the presence or absence of paracetamol (50 mg/kg i.p.) and/or caffeine were similar to values for afebrile cats
It is concluded that exogenous cyclic GMP and db cyclic GMP can inhibit central events mediating autonomic and behavioural thermoregulation stimulated in cats by exposure to cold environments.
THE ACTION OF LOPERAMIDE IN INHIBITING PROSTAGLANDIN‐INDUCED INTESTINAL SECRETION IN THE RAT
Authors: HARDCASTLE JACQUELINE , HARDCASTLE P.T. , READ N.W. , REDFERN J.S. 
Published: July 2012

The mechanisms by which loperamide inhibits the intestinal secretion induced by prostaglandin E2 were investigated in rat jejunum.
In vivo loperamide prevented prostaglandin‐induced fluid secretion but did not reduce the associated rise in the transintestinal potential difference.
In intestinal sheets the electrical response to prostaglandin E2 was enhanced in the presence of loperamide.
The ionic basis of these changes was determined by measuring Na+ and Cl− fluxes across intestinal sheets. Loperamide did not reduce the prostaglandin‐induced increase in net Cl− secretion, although it prevented the inhibition of mucosal‐to‐serosal Na+ movement.
Loperamide does not alter cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) levels by a direct action at the enterocyte, since in isolated enterocytes neither basal nor prostaglandin‐stimulated cyclic AMP levels were affected by the drug.
MECHANISM OF DECLINE IN RAT BRAIN 5‐HYDROXYTRYPTAMINE AFTER INDUCTION OF LIVER TRYPTOPHAN PYRROLASE BY HYDROCORTISONE: ROLES OF TRYPTOPHAN CATABOLISM AND KYNURENINE SYNTHESIS
Authors: YOUNG SIMON N. 
Published: July 2012

Two mechanisms have been proposed to explain the decline in brain tryptophan and 5‐hydroxytryptamine (5‐HT) after administration of hydrocortisone and the subsequent induction of liver pyrrolase. These are depletion of tryptophan by high rates of tryptophan catabolism and inhibition of tryptophan uptake by elevated levels of the tryptophan catabolite, kynurenine.
The increase in plasma kynurenine after hydrocortisone injection (25 mg/kg) was small, and kynurenine, at a concentration ten fold greater, did not inhibit tryptophan uptake by brain as measured by the Oldendorf technique. Thus, inhibition of tryptophan uptake by kynurenine is not an important mechanism in the control of brain tryptophan and 5‐HT.
The decline in brain tryptophan after hydrocortisone was comparable to that seen in other tissues, which comprise more than half of the body weight of a rat.
The total decline in free tryptophan stores in whole animals treated with hydrocortisone was estimated to be about 450 μg. This amount of tryptophan would be catabolized by tryptophan pyrrolase in about 20 min, when the enzyme is induced, according to an earlier estimate of the rate of tryptophan catabolism in vivo.
Tryptophan pyrrolase activity remains high for much longer than 20 min, suggesting that there is net protein catabolism, which releases tryptophan and prevents non‐protein tryptophan levels falling very far.
These results demonstrate that the decline in brain tryptophan and 5‐HT after hydrocortisone is caused by depletion of tryptophan stores due to the high activity of tryptophan pyrrolase. However, our data suggest that this effect is diminished by release of tryptophan from proteins. Thus, peripheral protein metabolism may be an important factor in the control of brain tryptophan levels and 5‐HT synthesis.
THE EFFECT OF THE CONVULSANT AGENT, CATECHOL, ON NEUROTRANSMITTER UPTAKE AND RELEASE IN RAT BRAIN SLICES
Authors: MINCHIN M.C.W. , PEARSON G. 
Published: July 2012

The effect of catechol on uptake and K+‐stimulated release of γ‐aminobutyric acid (GABA), D‐aspartate, noradrenaline and acetylcholine has been studied in slices of cerebral cortex and thalamus.
Low concentrations of catechol did not influence the uptake of any of the neurotransmitters in either brain area.
Noradrenaline release was unaffected by catechol.
Acetylcholine release from both cortical and thalamic slices was inhibited by high concentrations of catechol. This phenomenon is unlikely to be related to catechol‐induced convulsions.
Catechol (100 μm) inhibited GABA release from cortical slices by 28%. However, at a concentration of 10 μm catechol enhanced the release of D‐aspartate from thalamic slices by over 100%.
Potentiated release of excitatory amino acid transmitters may contribute to the enhanced excitability of thalamic cells which occurs during sensory myoclonus induced by low doses of catechol.
BINDING OF [3H]‐PRAZOSIN AND [3H]‐DIHYDROERGOCRYPTINE TO RAT CARDIAC α‐ADRENOCEPTORS
Authors: GUICHENEY PASCALE , MEYER PHILIPPE 
Published: July 2012

[3H]‐prazosin binds specifically to a single class of α‐adrenoceptors in rat cardiac membranes (KD25°C = 0.2 nM).
That these receptors are of the α1‐type was indicated by competition studies, i.e. α1‐antagonists such as prazosin and (2‐(2, 6‐dimethoxyphenoxyethyl) aminomethyl‐1, 4‐benzodioxane (WB 4101) were more potent than the α2‐antagonists, yohimbine and piperoxan in inhibiting [3H]‐prazosin binding.
A comparative study of [3H]‐prazosin binding and [3H]‐dihydroergocryptine binding to cardiac membranes showed that both [3H]‐prazosin and [3H]‐dihydroergocryptine (at low concentrations) bind to α1‐adrenoceptors, while [3H]‐dihydroergocryptine (at higher concentrations) also binds to another class of sites.
ACCUMULATION OF [3H]‐OUABAIN IN FUNCTIONALLY DIFFERENT CANINE CARDIAC TISSUES: DIFFERENTIAL Rb+ UPTAKE
Authors: RHEE H.M. 
Published: July 2012

In order to understand tissue‐specific differences in sensitivity to ouabain, the distribution of [3H]‐ouabain was investigated in seven functionally different, canine cardiac tissues.
Specialized cardiac tissues (e.g., pacemaker or conducting tissues) accumulate much less ouabain than do the contractile tissues such as the left ventricule or the papillary muscle.
This study confirms a greater Rb+ uptake in the Purkinje fibre than in the contractile tissue.
The results disprove the hypothesis that a high accumulation of ouabain in the Purkinje fibre is responsible for the well‐known sensitivity to ouabain in this tissue.