bluuebunny/crossref_metadata_2025 huggingface dataset:
THE CHOLINERGIC COMPONENT IN THE REFLEX VASODILATATION ELICITED BY STIMULATION OF THE DEPRESSOR NERVES IN THE RABBIT
Authors: CHIARIELLO M. , CONDORELLI M. , DE CAPRIO L. , RENGO F. , SACCÀ L. , TRIMARCO B.
Published: July 2012

The effects of the stimulation of the cephalic endings of the depressor nerve on the resistance in the perfused hindlimb were studied in the rabbit.

The vasodilatation thus elicited in the perfused hindlimb was reduced either by administration of guanethidine or by sympathectomy and abolished by subsequent treatment with atropine.

These data confirm the existence of two components in the genesis of the reflex vasodilatation: a passive component, due to the inhibition of sympathetic discharge, and an active component which in the rabbit is cholinergic in nature.
DECREASED PHENYLETHANOLAMINE‐N‐METHYLTRANSFERASE AND CATECHOL‐O‐METHYLTRANSFERASE ACTIVITY IN RABBIT ADRENAL GLANDS DURING PREGNANCY
Authors: PARVEZ H. , PARVEZ S. , RAZA‐BUKHARI A. , YOUDIM M.B.H.
Published: July 2012

Phenylethanolamine‐N‐methyltransferase (PNMT) activity in adrenal gland was lower than the control values at day 24 of rabbit pregnancy and fell throughout the gestational period.

Catechol‐O‐methyltransferase (COMT) activity during pregnancy and parturition followed a similar pattern to PNMT.

Adrenaline content of the adrenal gland declined significantly during the last few days of pregnancy but at parturition showed a tendency to return towards normal.

The biochemical mechanisms which result in a decline in PNMT and COMT activities and adrenaline concentration appear to be the consequence of modifications in endocrine gland secretion during pregnancy.
A COMPARISON OF d AND l‐TRYPTOPHAN ON THE CEREBRAL METABOLISM OF 5‐HYDROXYTRYPTAMINE AND DOPAMINE IN THE DOG
Authors: BUDNY J. , DOW R.C. , ECCLESTON D. , HILL A.G. , RITCHIE ISOBEL M.
Published: July 2012

After d and l‐tryptophan (50 mg/kg) were given intravenously in the dog, the concentration of the amino acid was increased in ventricular cerebrospinal fluid (CSF) during the subsequent 4 h of sampling, although the concentrations were significantly lower following the administration of the d‐isomer.

There was no evidence that d‐tryptophan increased the synthesis of 5‐hydroxytryptamine (5‐HT) in dog brain as judged by the failure to cause a change in 5‐hydroxyindoleacetic acid (5‐HIAA) concentrations in ventricular CSF different from that seen with controls.

There was no appreciable conversion of d‐tryptophan to l‐tryptophan in the dog.

d‐tryptophan was cleared more rapidly from plasma than l‐tryptophan.

No difference in plasma binding between d and l‐tryptophan was detected.
DETERMINATION OF HALOTHANE‐INDUCED SLEEPING TIME IN THE RAT: EFFECT OF PRIOR ADMINISTRATION OF CENTRALLY ACTIVE DRUGS
Authors: TURNBULL M.J. , WATKINS J.W.
Published: July 2012

A method is described for the determination of halothane‐induced sleeping time in the rat.

The sleeping time exhibited a diurnal variation which was due, at least in part, to a change in the sensitivity of the central nervous system (CNS) to the anaesthetic.

Tolerance to halothane did not develop in rats repeatedly exposed to the anaesthetic over a period of over 48 hours.

Repeated sleeping time determinations have been used to follow changes in the sensitivity of the CNS to the anaesthetic occurring with time.

A tolerance to halothane was induced by pretreatment of rats with doses of amylobarbitone, pentobarbitone or meprobamate sufficient to keep animals anaesthetized for approximately 12 hours. This tolerance was followed by a period of halothane‐hypersensitivity.

Halothane‐tolerant animals awakened with higher brain halothane concentrations and were also tolerant to intracerebroventricularly administered pentobarbitone.

Halothane‐hypersensitive rats awakened with lower brain halothane concentrations and were also hypersentive to intracerebroventricularly administered pentobarbitone.

The possibility that the induction of cross‐tolerance to halothane may be indicative of a drug's potential to produce dependence is discussed.
ADRENOCEPTORS OF THE GUINEA‐PIG URINARY BLADDER
Authors: DAVE K.C. , DHATTIWALA A.S.
Published: July 2012

Adrenaline, noradrenaline and isoprenaline (5 μg/ml) did not affect the resting tone of the isolated urinary bladder of the guinea‐pig.

The catecholamines (1–2 μg/ml) inhibited neuronally evoked contractions at various stimulation frequencies; the inhibition was maximum at 2 Hz and minimum at 50 Hz. Isoprenaline produced maximum inhibition.

Propranolol (0.5 μg/ml) completely blocked the catecholamine‐induced inhibition at all the frequencies employed. The concentration‐response curves of isoprenaline at 2, 10 and 50 Hz were characteristically shifted by propranolol (50 ng/ml). Phenoxybenzamine (0.2 μg/ml) was totally ineffective.

In some experiments adrenaline significantly raised the tone of the bladder exposed to propranolol; this effect could be blocked by phenoxybenzamine.

Acetylcholine‐induced bladder contractions were inhibited by adrenaline (2 μg/ml); the inhibition was completely blocked by propranolol (0.5 μg/ml).

The results indicate the presence of an inhibitory β‐adrenoceptor and suggest the possibility of an excitatory α‐adrenoceptor in guinea‐pig urinary bladder.
THE ACTION OF TETRAETHYL‐AMMONIUM CHLORIDE ON THE RESPONSE OF THE RAT ANOCOCCYGEUS MUSCLE TO MOTOR AND INHIBITORY NERVE STIMULATION AND TO SOME DRUGS
Authors: GILLESPIE J.S. , TILMISANY A.K.
Published: July 2012

Tetraethylammonium chloride (TEA) 0.125 mm to 20 mm potentiates the response of the anococcygeus muscle to field stimulation of the motor adrenergic nerves without affecting the response to noradrenaline suggesting a pre‐synaptic origin of potentiation. The potentiation is greatest at low, submaximal, frequencies (2 Hz) of stimulation and only slight at the higher frequency of 20 Hz. This difference is due to the restraint imposed on the demonstration of potentiation by maximal or near maximal motor responses since reduction of the mechanical response at 20 Hz by either phentolamine (post‐synaptic block) or guanethidine (pre‐synaptic block) resulted in a great increase in potentiation of the response at this frequency.

TEA in concentrations up to 1 mm similarly potentites the response to inhibitory nerve stimulation and again the greatest effect is at low frequencies. Higher concentrations (5–20 mm) progressively depress the inhibitory response. It is suggested that TEA may specifically antagonize the post‐synaptic action of the inhibitory transmitter and that at higher concentrations of TEA this effect dominates the pre‐synaptic action in increasing transmitter release.

TEA has no effect on the motor response to tyramine.

TEA (5–20 mm) causes a maintained rise in muscle tone. Part of this is abolished by phentolamine but part is resistant. A similar muscle stimulant action of TEA is observed in muscles from rats previously treated with 6‐hydroxydopamine in which indirect sympathomimetic drugs and field stimulation could no longer produce a motor response. These results suggest that part of the motor effect of TEA is due to an increased spontaneous release of noradrenaline and part to a direct action on the muscle.

TEA 0.125 mm to 20 mm antagonize the stimulant action of carbachol. Dose‐response curves show a parallel shift to the right with no change in the maximum response suggesting a competitive atropine‐like action. Such an effect has previously been reported in amphibian tissue but not so far as we can determine in mammalian preparations.

The possible mode of action of TEA is discussed.
THE EFFECT OF HIGH RATES OF VASOPRESSIN ADMINISTRATION ON RENAL POTASSIUM AND SODIUM EXCRETION DURING POTASSIUM LOADING IN THE SHEEP
Authors: BEAL A.M.
Published: July 2012

The influence of potassium loading on the renal excretion of sodium, potassium and solute during high rate vasopressin administration has been investigated in sheep.

Adrenalectomized sheep were infused with 0.43 m KCl at 2 ml/min for 2–2.5 hours. Coincident with the rise in plasma potassium concentration, the urinary excretion of sodium, potassium, solute and water was increased as was the reabsorption of solute‐free water. The rates of urinary excretion of sodium and potassium, osmolal clearance (COsm) and solute‐free water reabsorption (TcH2O) for the first 50 min of potassium infusion were each found to be linearly related to the plasma potassium concentration.

After 50 min an infusion of vasopressin at 1 or 4 mu/min was superimposed on the potassium infusion for a period of 30 minutes. The administration of vasopressin was consistently associated with further augmentation of potassium excretion and clearance, of osmolal clearance and of solute‐free water reabsorption to values above those anticipated from the pre‐vasopressin regression lines for these parameters. Urinary sodium showed a coincident depression in the rate of excretion and clearance during the same period.

Thirty to fifty minutes after the cessation of vasopressin infusion the potassium and sodium excretions had returned to values which approximated the pre‐vasopressin relations between plasma potassium and the urinary excretions of these ions.

Both rates of vasopressin infusion were equally effective in increasing the potassium clearance. Any differences in clearance between the two rates of vasopressin administration were not statistically significant.

The large increments in potassium excretion (averaging > 40%) were interpreted as indicating that, when vasopressin is present at high concentrations, the distal tubule is one site of action of the hormone in the nephron of sheep.
THE RELEASE OF A CORONARY VASODILATOR METABOLITE FROM THE GUINEA‐PIG ISOLATED PERFUSED HEART STIMULATED BY CATECHOLAMINES, HISTAMINE AND ELECTRICAL PACING AND BY EXPOSURE TO ANOXIA
Authors: BROADLEY K.J.
Published: July 2012

A procedure involving two guinea‐pig isolated hearts perfused in series is described for detecting in the recipient heart the release of a possible coronary vasodilator metabolite from the donor heart.

Adrenaline and isoprenaline stimulated the rate and force of contraction and produced a multiphasic coronary vascular response, the predominant phase of which was vasodilatation. When the β‐adrenoceptors of the recipient heart were blocked, stimulation of the donor heart by the catecholamines was associated with a coronary vasodilatation of the recipient heart.

Histamine stimulated rate and force of contraction and was predominantly coronary vasodilator. After blockade of histamine H1‐and H2‐receptors in the recipient heart, coronary vasodilatation followed increases in activity of the donor heart in response to histamine.

These vasodilator responses of the recipient heart were attributed to the release from the donor heart of a vasodilator metabolite by the increased activity. This is the proposed mechanism for the predominant coronary vasodilator response to catecholamines and histamine.

Periods of electrically‐paced tachycardia and anoxia of the donor heart also led to the release of vasodilator activity.

The possible identity of the metabolite is discussed.
MORPHINE–NALOXONE INTERACTION IN THE CENTRAL CHOLINERGIC SYSTEM: THE INFLUENCE OF SUBCORTICAL LESIONING AND ELECTRICAL STIMULATION
Authors: JHAMANDAS K. , SUTAK M.
Published: July 2012

The opiate antagonist naloxone, injected or topically applied to the cerebral cortex, had no significant effect on the spontaneous output of cortical acetylcholine (ACh) in rats.

Morphine (2.5 mg/kg) administered intravenously inhibited the release of cortical ACh. A subsequent injection of naloxone rapidly reversed morphine‐induced inhibition, and produced a sustained increase in the release of ACh. Topical application of naloxone solutions, after morphine, produced a slow and weak reversal of its inhibitory action.

Destruction of the medial thalamus abolished both the inhibitory effects of morphine on the cortical ACh release, and its antagonism by naloxone administered after the agonist.

Injection of naloxone in a low dose (0.1 mg/kg) increased the release of cortical ACh provoked by electrical stimulation of either the medial thalamus or the reticular formation in normal rats. In the morphine‐dependent rat, naloxone also facilitated the evoked release and its action was greater than in control animals. The facilitatory effect of naloxone on the cortical release evoked by stimulation of the medial thalamus was greater than its effect on the release evoked by stimulation of the reticular formation in both normal and morphine‐dependent rats.

Naltrexone, a narcotic antagonist, also facilitated the electrically stimulated release of cortical ACh.

It is suggested that (a) morphine and naloxone act at a subcortical site, probably the medial thalamus, to modify the cortical ACh release and that (b) naloxone may facilitate the electrically‐induced release of ACh in the CNS by antagonizing the effect of the endogenous morphine‐like factor, enkephalin.
EFFECTS OF l‐TRYPTOPHAN AND l‐METHIONINE ON ACTIVITY IN THE RAT
Authors: TAYLOR M.
Published: July 2012

The effects of an intraperitoneal dose of 20 mg/kg L‐tryptophan and doses of 100 and 150 mg/kg of l‐methionine were investigated on activity in the rat.

Activity was measured by a time sampling behaviour categorization procedure, and began 15 min after compound administration, lasting for a total of one hour.

Total active behaviour in the first half hour was reduced after 20 mg/kg tryptophan, 100 or 150 mg/kg methionine. Only 20 mg/kg tryptophan led to a significant reduction in active behaviour during the second half hour.

Administration of 100 mg/kg methionine plus 20 mg/kg tryptophan, and 150 mg/kg methionine plus 20 mg/kg tryptophan had no discernible effect on activity.

The results draw attention to the role of another amino acid in the modification of the behavioural effects of tryptophan.
THE EFFECT OF METIAMIDE ON ACID SECRETION STIMULATED BY GASTRIN, ACETYLCHOLINE AND DIBUTYRYL CYCLIC ADENOSINE 3′, 5′‐MONOPHOSPHATE IN THE ISOLATED WHOLE STOMACH OF THE RAT
Authors: BUNCE K.T. , PARSONS M.E. , ROLLINGS NITA A.
Published: July 2012

An isolated stomach preparation from immature rats is described. The lumen of the stomach was perfused and the hydrogen ion activity of the perfusate recorded continuously.

The preparation gave dose‐dependent responses to gastrin, acetylcholine and dibutyryl cyclic adenosine 3′,5′‐monophosphate and these responses were readily reversed on washing out the agonist.

The acid secretory response to gastrin was inhibited by metiamide at concentrations of 10−5 M and 3 × 10−5 m.

The acid secretory responses to acetylcholine and dibutyryl cyclic adenosine 3′,5′‐monophosphate were not inhibited by concentrations of metiamide up to 10−3 m.

These findings are discussed in relation to the role of histamine in the control of gastric acid secretion.
ACTION OF SURUGATOXIN ON NICOTINIC RECEPTORS IN THE SUPERIOR CERVICAL GANGLION OF THE RAT
Authors: BROWN D.A. , GARTHWAITE J. , HAYASHI E. , YAMADA S.
Published: July 2012

Surugatoxin (SGTX, 0.1–2 μm) reversibly depressed orthodromic transmission and antagonized the depolarizing action of carbachol on the isolated superior cervical ganglion of the rat. The apparent dissociation equilibrium constant against carbachol‐induced depolarization (measured in the presence of hyoscine) was 58 and 76 nm determined at 0.2 and 2 μm respectively. SGTX (2 μm) did not reduce the depolarizing effects of (±)‐muscarine, γ‐aminobutyric acid or angiotensin, but did reduce that to 5‐hydroxytryptamine. Release of [3H]‐acetylcholine following repetitive (10 Hz) preganglionic sympathetic stimulation was maintained in the presence of 2 μm SGTX. It is concluded that SGTX has a high and selective affinity for ganglionic nicotinic receptors.
CARDIOVASCULAR EFFECTS OF DOPAMINE AFTER CENTRAL ADMINISTRATION INTO CONSCIOUS CATS
Authors: DAY M.D. , ROACH A.G.
Published: July 2012

Dopamine (30 and 45 μg) administered intracerebroventricularly (i.c.v.) to a group of 10 conscious normotensive cats caused dose‐related increases in blood pressure and heart rate. In 4 of these animals the initial cardiovascular stimulant effects of i.c.v. dopamine were followed by hypotension and bradycardia.

α‐Methyldopamine (30 and 45 μg i.c.v.) produced qualitatively similar responses to dopamine except that the cardiovascular stimulant effects were smaller and the secondary depressant effects somewhat more prolonged.

Both stimulant and depressant effects of i.c.v. dopamine and α‐methyldopamine were greatly inhibited by autonomic ganglion blockade or by adrenergic neurone blockade.

The cardiovascular stimulant effects of both i.c.v. dopamine and i.c.v. α‐methyldopamine were selectively inhibited by β‐adrenoceptor blocking agents whilst the cardiovascular depressant effects of these substances were abolished by the α‐adrenoceptor blocker phentolamine or by the dopamine‐β‐hydroxylase inhibitor disulfiram.

Haloperidol by either i.c.v. or the intravenous route abolished both cardiovascular stimulant and depressant effects of i.c.v. dopamine, whilst pimozide by either route inhibited only the cardiovascular stimulant effects.

In 2 cats, injection of dopamine into the cisterna magna produced predominantly depressant effects on the cardiovascular system except with a higher dose which induced biphasic responses.
INHIBITION BY AMILORIDE OF SODIUM‐DEPENDENT FLUID REABSORPTION IN THE RAT ISOLATED CAUDAL EPIDIDYMIS
Authors: WONG P.Y.D. , YEUNG C.H.
Published: July 2012

The rate of fluid reabsorption was studied in the rat isolated caudal epididymal sac in vitro.

Part of the fluid reabsorption was found to be dependent on intraluminal Na+. Amiloride (0.1 mm) completely inhibited this component of fluid reabsorption.

The log dose‐inhibition curve to amiloride was sigmoid and the IC50 value was found to be 1.6 μm.
THE EFFECT OF A NEW ANTI‐INFLAMMATORY DRUG, FLURBIPROFEN, ON THE RESPIRATORY, HAEMODYNAMIC AND METABOLIC RESPONSES TO E. coli ENDOTOXIN SHOCK IN THE CAT
Authors: PARRATT J.R. , STURGESS R.M.
Published: July 2012

The intravenous administration of E. coli endotoxin (2.0 mg/kg) in cats anaesthetized with sodium pentobarbitone resulted in immediate pulmonary hypertension and reductions in lung compliance and systemic arterial Po2. These effects were abolished, or greatly reduced, by the prior intravenous administration of flurbiprofen in doses (100 and 250 μg/kg and 1.0 mg/kg) which were devoid of cardiovascular or metabolic effects. Flurbiprofen is thus the most active antipyretic‐analgesic drug so far examined in this experimental model.

Production of lactate, characteristic of the severe, secondary endotoxin shock phase, was delayed only by the highest dose of flurbiprofen; hypotension, hypoglycaemia and the reduction in cardiac output which occurs during this phase, were unaffected.

These findings are discussed with reference to the treatment of the ‘shocked lung’ syndrome of human septicaemia.
STUDIES ON THE MECHANISM OF ACTION OF AMANTADINE
Authors: BROWN F. , REDFERN P.H.
Published: July 2012

The effect of amantadine hydrochloride on various aspects of catecholamine metabolism in the rat brain has been investigated.

Amantadine failed to have any significant effect on brain concentrations of dopamine or noradrenaline even when administered daily for 9 days.

Amantadine had no effect on the rate of decline of noradrenaline and dopamine concentrations after α‐methyl‐p‐tyrosine.

In vitro, amantadine inhibited dopamine uptake into synaptosomes only at high concentrations, and caused little release of dopamine from synaptosomes.

There is no evidence from these results to suggest that the anti‐Parkinsonian effect of amantadine is related to an action on dopaminergic mechanisms.
THE EFFECTS OF pH ON THE ACTIVITY OF CORYNEINE AND RELATED PHENOLIC QUATERNARY AMMONIUM SALTS ON THE FROG RECTUS PREPARATION
Authors: BARLOW R.B.
Published: July 2012

The activity of m‐hydroxybenzyltrimethylammonium, coryneine (3:4‐dihydroxyphenethyl‐trimethylammonium, ‘quaternary dopamine’), and m‐hydroxyphenylpropyltrimethylammonium relative to tetramethylammonium has been measured on the frog rectus preparation (Rana pipiens) at pH 7 and pH 9.

The compounds are more active in the more acid environment indicating that ionization of the phenolic group reduces activity to between one‐half and one‐tenth of that of the form with the intact hydroxyl group.

In contrast with the situation at aminoacid receptors, there is no reason to believe that at other receptors zwitterions are likely to be more active than the uncharged forms with which they are in equilibrium.
INTERACTIONS OF ISOPRENALINE AND PROSTAGLANDIN E2 WITH RESPECT TO MYOCARDIAL CONTRACTILE FORCE, CORONARY VASCULAR RESISTANCE AND MYOCARDIAL OXYGEN CONSUMPTION IN GUINEA‐PIG ISOLATED HEARTS
Authors: KREBS R. , SCHRÖR K.
Published: July 2012

Left ventricular pressure (LVP), left ventricular pressure derivative (LV dp/dtmax), coronary vascular resistance (CVR) and myocardial oxygen consumption (Qo2) were measured simultaneously in isolated, electrically driven hearts of guinea‐pigs at constant perfusion rate.

LVP, LV dp/dtmax, CVR and Qo2 were greatly decreased by either the addition of prostaglandin E2 (50 ng/ml) to the perfusion fluid or pretreatment of the animals with reserpine.

Isoprenaline (0.5 nm to 100 nm) induced increases in LVP, LV dp/dtmax. and Qo2. In the presence of prostaglandin E2, there was a parallel shift of the isoprenaline concentration‐response curve for LVP and LV dp/dtmax. This effect was not seen, after the animals had been treated with reserpine.

Qo2 was also decreased by prostaglandin E2 only in non‐reserpine treated animals.

CVR was diminished by isoprenaline in the untreated group. However, there was increase in CVR, when isoprenaline was added to either prostaglandin E2 or reserpine‐pretreated hearts which was enhanced in the reserpine plus prostaglandin E2‐treated group (P < 0.01).

The results give evidence for different actions of prostaglandin E2 on isoprenaline concentration‐response curves for LVP, LV dp/dtmax and CVR.
EFFECT OF IONOPHORE X‐537A ON DESENSITIZATION RATE AND TENSION DEVELOPMENT IN POTASSIUM‐DEPOLARIZED MUSCLE FIBRES
Authors: DeBASSIO W.A. , PARSONS R.L. , SCHNITZLER R.M.
Published: July 2012

The effects of the ionophore X‐537A were studied on carbamylcholine (carbachol)‐induced desensitization and on tension development in relaxed potassium‐depolarized frog sartorius muscles.

X‐537A accelerated carbachol‐induced desensitization in Ca2+‐deficient solutions without having any effect on the conductance of the membrane in the absence of carbachol or on the extent of the carbachol‐induced increase in conductance.

In Ca2+‐deficient solution, the acceleration of desensitization by the ionophore was concentration‐dependent. No effect was observed with concentrations less than 5 μm and maximal acceleration was evident with 10 μm.

The influence of X‐537A on desensitization was time‐dependent. At 20 μm X‐537A, there was a marked acceleration of desensitization by the end of 5 min exposure. An additional gradual acceleration occurred during a 5 to 30 min treatment. No acceleration of desensitization was evident when X‐537A was simultaneously applied with carbachol to the end‐plate region without prior exposure to the ionophore.

Desensitization also was accelerated by 30 min exposure to 20 μm X‐537A in solutions containing Ca2+ or deficient in both Mg2+ and Ca2+; the rate being increased 2.8‐fold in Ca2+‐containing solutions, 2.9‐fold in Ca2+‐deficient solutions containing Mg2+, and 2.5‐fold in divalent cation‐deficient solutions.

Tension development gradually occurred in relaxed potassium‐depolarized muscle preparations exposed to 20 μm X‐537A. The onset of tension development occurred only after approximately 25 min of exposure both in preparations kept in Ca2+‐deficient or Ca2+‐containing solutions. By the end of 90 min in the ionophore, the tension developed was approximately 12% and 23% of the initial potassium contracture in those preparations maintained in the Ca2+‐deficient or Ca2+‐containing solutions, respectively.

We assume that the increase in desensitization rate following exposure to X‐537A results from an elevation of the intracellular Ca2+ concentration. That muscle tension gradually increased during exposure to the ionophore supports this conclusion. The acceleration of desensitization by X‐537A in the absence of external Ca2+ supports the view that the site of calcium acceleration is not on the external surface of the end‐plate membrane either at or near the agonist‐recognition site but rather on the inner surface.
ON THE DECREASE OF MYOCARDIAL OXYGEN CONSUMPTION INDUCED BY CHLORACYZINE
Authors: KISIN I.E.
Published: July 2012

The effects of chloracyzine (2‐chloro‐10‐(3‐diethylaminopropionyl)‐phenothiazine hydrochloride; antianginal drug) on myocardial oxygen consumption were studied in open‐chest cats and cat isolated hearts using oximetry and polarography respectively.

It was found that chloracyzine produced a decrease in myocardial oxygen consumption accompanied by a reduction in coronary blood flow preceded by transient coronary dilatation. Chloracyzine produced an insignificant increase in arterial pressure; heart rate increased slightly in the open‐chest experiments but not in the isolated heart.

It is suggested that reduced oxygen uptake after chloracyzine is realized through improved efficiency in the use of oxygen.
EFFECT OF INDOMETHACIN AND PROSTAGLANDIN ON THE SMOOTH MUSCLE CONTRACTING ACTIVITY OF ANGIOTENSIN AND OTHER AGONISTS
Authors: ABOULAFIA JEANNINE , MENDES GUN B. , MIYAMOTO MARIA E. , PAIVA A.C.M. , PAIVA THEREZINHA B.
Published: July 2012

Indomethacin had an equal inhibitory effect on the response of the guinea‐pig isolated ileum to angiotensin II (angiotensin), bradykinin, histamine and acetylcholine. This effect did not seem to result from inhibition of prostaglandin synthesis, as it did not depend on the time of treatment with indomethacin.

Prostaglandin E2 (prostaglandin) potentiated the responses of the guinea‐pig ileum to angiotensin, bradykinin, histamine and acetylcholine without significant differences in the effects observed.

In the rabbit isolated mesenteric and coeliac arteries, indomethacin had an equal potentiating effect on the responses to angiotensin and to adrenaline. In these organs pre‐incubation with indomethacin was necessary for the effect to be observed, and this effect lasted for 2 h or more after that drug was removed from the medium.

No cross‐tachyphylaxis between angiotensin and adrenaline was observed in the rabbit mesenteric and coeliac arteries.

It is concluded that the effects of indomethacin and prostaglandin on the response of the guinea‐pig ileum to the four agonists result from an action on the smooth muscle contractile mechanism per se rather than from an inhibitory action on the release of endogenous prostaglandin produced by the four agonists.

The results with the rabbit isolated arteries indicate that tachyphylaxis to angiotensin in these organs is not caused by prostaglandin release.
THE ACTION OF MICRO‐ELECTROPHORETICALLY APPLIED 1‐3,4‐DIHYDROXYPHENYLALANINE (DOPA) ON SINGLE CORTICAL NEURONES
Authors: BEVAN P. , BRADSHAW C.M. , SZABADI E.
Published: July 2012

The technique of microelectrophoresis was used in order to compare the actions of l‐3,4‐dihydroxyphenylalanine (DOPA) and noradrenaline on single neurones in the cerebral cortices of cats and rats.

DOPA could both excite and depress cortical neurones. Cells excited by DOPA were also excited by noradrenaline and cells depressed by DOPA were also depressed by noradrenaline.

In the case of both excitatory and depressant responses, DOPA appeared to be less potent than noradrenaline.

Responses to DOPA and noradrenaline could be antagonized by phentolamine and propranolol. Responses to acetylcholine were not affected.

Responses to acetylcholine, but not responses to DOPA, were antagonized by atropine.

The results indicate that locally applied DOPA may mimic the actions of noradrenaline on cortical neurones. Possible mechanisms for these effects of DOPA are discussed.
THE LACK OF EFFECT OF OXYTETRACYCLINE ON RESPONSES TO SYMPATHETIC NERVE STIMULATION AND CATECHOLAMINES IN VASCULAR TISSUE
Authors: KALSNER S.
Published: July 2012

The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined.

Oxytetracycline (0.1 mm) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5–10 Hz) or noradrenaline (0.5–50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline.

Oxytetracycline (0.1 mm) did not alter the position or shape of the concentration‐response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips.

It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue.
DOPAMINE AND THE DEPRESSANT ACTION OF MORPHINE ON STIMULATED GUINEA‐PIG ILEUM
Authors: FERRI S. , REINA R. , SANTAGOSTINO A.
Published: July 2012

Morphine reduces the amplitude of the contractions induced by electrical stimulation, in the myenteric plexus‐longitudinal muscle preparation of guinea‐pig ileum. Dopamine and apomorphine have the same effect but at much higher concentrations.

Dopamine, at concentrations lower than those which would normally be inhibitory, partially reverses the depressant effect of morphine.

Pre‐treatment of guinea‐pigs with 6‐hydroxydopamine results in a slight supersensitivity of innervated longitudinal muscle preparations to dopamine and has no effect on morphine activity.

Naloxone antagonizes the depressant effect of morphine but not that of dopamine or apomorphine.

The response of the ileum preparation to morphine is not affected by phentolamine or propranolol; the effect of dopamine, however, is abolished by α‐adrenoceptor blockade.
STRUCTURE‐ACTIVITY RELATIONSHIP OF VARIOUS CORTICOSTEROIDS ON THE FEEDBACK CONTROL OF CORTICOTROPHIN SECRETION
Authors: JONES M.T. , TIPTAFT ELIZABETH M.
Published: July 2012

Several steroids occurring in the pathway of corticosteroid biosynthesis were investigated for their ability to exert a fast or delayed feedback inhibition of stress‐induced release of corticotrophin. Rats were injected subcutaneously with vehicle or a steroid either 10 min (fast feedback) or 4 h (delayed feedback) before they were subjected to stress which consisted of a 2 min exposure to ether vapour.

Changes in plasma corticosterone concentration and in vitro corticosterone production by excised adrenal glands were used as indices of corticotrophin release.

Among the steroids tested only 11β, 21‐dihydroxypregn‐4‐ene‐3, 20‐dione (corticosterone) and 11β, 14α, 21‐trihydroxypregn‐4‐ene‐3, 20‐dione (cortisol) inhibited the stress response 10 min after their administration. Therefore, it appears that the fast feedback mechanism is limited to steroids with a 21‐hydroxyl and a 11β‐hydroxyl group.

In contrast, many steroids caused inhibition of the stress response 4 h after their administration. These steroids were corticosterone, cortisol, 21‐hydroxypregn‐4‐ene‐3, 20‐dione (11‐deoxycorticosterone), 17α, 21‐dihydroxypregn‐4‐ene‐3, 20‐dione (11‐deoxycortisol), 11β‐hydroxypregn‐4‐ene‐3, 20‐dione (11β‐hydroxyprogesterone) and 11β, 17α‐dihydroxypregn‐4‐ene‐3, 20‐dione (11β, 17α‐dihydroxyprogesterone). Thus, either the 21‐hydroxyl group (e.g. 11‐deoxycorticosterone) or the 11β‐hydroxyl group (e.g. 11β‐hydroxyprogesterone) is sufficient for delayed feedback activity. The 11α‐hydroxyl group, e.g. 11α, 17α, 21‐trihydroxypregn‐4‐ene‐3, 20‐dione (11‐epicortisol) renders the steroid inactive on both feedback mechanisms.

18, 21‐Dihydroxypregn‐4‐ene‐3, 20‐dione (18‐hydroxydeoxycorticosterone) was found to be the only steroid that is secreted by the adrenal gland of the rat in quantities sufficient to cause exaggeration of the stress‐induced release of corticotrophin. This steroid has been implicated as a possible hypertensive agent, and its role in the control of corticotrophin secretion is discussed here.
SELECTIVE RESERPINE‐INDUCED SUPERSENSITIVITY OF THE POSITIVE INOTROPIC AND CHRONOTROPIC RESPONSES TO ISOPRENALINE AND SALBUTAMOL IN GUINEA‐PIG ISOLATED ATRIA
Authors: BROADLEY K.J. , LUMLEY P.
Published: July 2012

Dose‐response curves for the positive inotropic and chronotropic responses to isoprenaline were obtained in atria from untreated guinea‐pigs and those receiving various reserpine pretreatments.

Tension responses were unaffected, whereas rate responses were depressed by the lowest dose of reserpine (0.05 mg/kg i.p. at 24 hours).

With larger 24 h doses and a 3 day pretreatment, the rate and tension dose‐response curves were progressively displaced to the left, indicating supersensitivity which was greater for tension at each pretreatment.

No supersensitivity to histamine or Ca2+ could be detected, leading to the conclusion that it was selective for the β‐adrenoceptor agonists possibly at the receptor level.

As an indication of the adrenergic neurone depleting effectiveness of each reserpine dosage, preparations were exposed to test doses of β‐phenylethylamine.

Salbutamol was a partial agonist in untreated atria, the maximum rate (63.3%) and tension (10.0%) responses being less than those for isoprenaline. In atria from reserpine pretreated animals the supersensitivity was revealed as an increase of this maximum compared with isoprenaline.

The significance of this observation in relation to the possible mechanism of the supersensitivity is discussed.
NICOTINE STIMULATES PROSTAGLANDIN FORMATION IN THE RABBIT HEART
Authors: WENNMALM Å.
Published: July 2012

Rabbit isolated hearts were perfused according to Langendorff with Tyrode solution. Prostaglandin‐like substances (PLS) in the effluent were purified and assayed on the rat stomach strip. Noradrenaline (NA) in the effluent was assayed fluorimetrically.

Infusion of nicotine (1 μm‐50 μm) caused a dose‐dependent, brief increase, from 1.2 ± 0.4 to maximally 8.3 ± 2.1 ng/min, in the outflow of PLS from the heart. The increase was abolished by pretreatment of the heart with indomethacin.

Activation of nicotinic receptors in the heart with acetylcholine (ACh, 200 μm) in the presence of atropine (1 μm) also elicited an increase in the release of PLS. This release was smaller than that caused by nicotine.

Nicotine (50 μm) and ACh (200 μm) in the presence of atropine (1 μm) each caused a pronounced but brief release of NA into the effluent. There was no evident correlation between the ability of the drugs to cause release of PLS on the one hand, and NA on the other.

It is concluded that nicotine acts as a direct stimulus for the synthesis of prostaglandins in the rabbit heart.
ACCUMULATION OF RADIOACTIVE CARDIAC GLYCOSIDES BY VARIOUS BRAIN REGIONS IN RELATION TO THE DYSRHYTHMOGENIC EFFECT
Authors: DUTTA S. , MARKS B.H. , SCHOENER E.P.
Published: July 2012

Ouabain was administered at a loading dose of 3 μg/kg followed by an infusion at a rate of 1 μg kg−1 min−1 in order to produce severe dysrhythmia in dogs within 60 minutes. Similarly, digitoxin at a loading dose of 9 μg/kg followed by an infusion at a rate of 3 μg kg−1 min−1 was administered to compare its effect with that of ouabain.

During the 60 min experimental period, the plasma concentrations gradually rose with the continuous infusion of these drugs. However, in comparison to the 60 min plasma value of 119 ± 20 pmol/ml for ouabain and 177 ± 68 pmol/ml for digitoxin, the cerebrospinal fluid (CSF) concentrations for these drugs at this time were less than 5 pmol/ml.

Upon termination of the experiment at 60 min it was found that kidney, liver, heart, adrenal, and the non‐neural tissue in the brain such as pituitary and choroid plexus concentrated ouabain and digitoxin to give high tissue to plasma ratios. However, various neural areas of the brain (cerebellum, mesencephalon, hypothalamus, pons, and medulla) showed no preferential localization or uptake of these two glycosides.

Concentration of ouabain and digitoxin by the choroid plexus does not seem to affect the ionic composition of the CSF.

It was concluded that sampling the large areas of neural tissue listed above could provide no evidence for local accumulation of digitalis glycosides that might account for a central nervous system origin of digitalis‐induced cardiac arrhythmias.
DIFFERENTIATION OF METABOLIC ADRENOCEPTORS
Authors: LOAKPRADIT T. , LOCKWOOD R.
Published: July 2012

Cardiovascular and metabolic responses to intravenous infusion of isoprenaline were measured in fasted, anaesthetized cats.

Isoprenaline (0.2 μg kg−1 min−1 for 15 min) decreased diastolic blood pressure and increased heart rate, blood glucose, blood lactate and plasma free fatty acids.

Oxprenolol (0.5 mg/kg) antagonized all cardiovascular and metabolic effects of isoprenaline non‐selectively.

Para‐oxprenolol (0.25 mg/kg) and practolol (4 mg/kg) antagonized the effects of isoprenaline on heart rate and free fatty acids selectively.

H 35/25 ((1‐(4‐methylphenyl)‐2‐isopropyl aminopropanol) hydrochloride, 3 mg/kg) antagonized the effects of isoprenaline on blood pressure, glucose and lactate selectively.

It is concluded that metabolic adrenoceptors are differentiated into subtypes similar to those mediating cardiostimulation and vasodilatation.
ROLE OF 5‐HYDROXYTRYPTAMINE IN MORPHINE‐, PETHIDINE‐, AND METHADONE‐INDUCED HYPOTHERMIA IN RATS AT LOW AMBIENT AND ROOM TEMPERATURE
Authors: OKA T.
Published: July 2012

1 The effect of morphine (10 or 20 mg/kg s.c.), pethidine (25 or 50 mg/kg s.c.) or methadone (4 or 8 mg/kg s.c.) on the body temperature of nontreated and p‐chlorophenylalanine‐pretreated rats was studied at room (21 ± 0.2°C) or low ambient (12 ± 0.2°C) temperature.

2 Neither pethidine nor smaller doses of morphine and methadone altered the mean rectal temperature of rats kept at room temperature but larger doses of morphine and methadone produced significant hypothermia.

3 All narcotic analgesics at doses used in the present investigation produced significant hypothermia in rats maintained in a low ambient temperature. The hypothermia was prevented by naloxone (1 mg/kg s.c.).

4 The administration of p‐chlorophenylalanine (PCPA, 320 mg/kg i.p.) 48 h before the narcotic injection prevented the fall in body temperature both at room and low ambient temperature.

5 The administration of narcotic analgesics at doses, which when administered by themselves did not alter the body temperature of rats, produced significant hyperthermia in rats pretreated with PCPA.

6 When rats pretreated with PCPA were given 5‐hydroxytryptophan (75 mg/kg s.c.) 30 min before narcotic administration, the usual response to narcotics was restored.

7 It appears that pethidine and methadone as well as morphine have both hyperthermic and hypothermic actions in rats and that 5‐hydroxytryptamine may be involved in the narcotic‐induced hypothermia not only at room temperature but also at low ambient temperature.
EFFECT OF TWO HEMICHOLINIUMS ON THE DISPOSITION AND DISTRIBUTION OF ENDOGENOUS FREE CHOLINE IN ANAESTHETIZED RABBITS
Authors: GARDINER J.E. , GWEE M.C.E.
Published: July 2012

1 The effects of hemicholinium no. 3 (HC‐3) and its p‐terphenyl analogue (TPHC‐3) on the disposition and distribution of free choline were studied in rabbits under pentobarbitone anaesthesia. Free choline was determined by bioassay.

2 The respiration of animals given 0.35 μmol/kg of HC‐3 was hardly affected; however, 4 out of 6 rabbits given the same dose of TPHC‐3 exhibited varying degrees of respiratory impairment. All animals that received 2 injections (1 h apart) of either HC‐3 (1.4 μmol/kg) or TPHC‐3 (0.7 μmol/kg) developed respiratory difficulty about 1 h after the second injection.

3 The respiratory distress was accompanied by a 2 to 15‐fold rise in plasma choline concentration. This rise has been attributed to hypoxia.

4 In experiments in which choline has been infused it was observed that HC‐3 could impair the animal's ability to dispose of exogenous choline. In control rabbits neither HC‐3 nor TPHC‐3 produced changes in plasma choline concentrations unless the respiration was depressed.

5 Either HC‐3 or TPHC‐3 (both at 0.35 μmol/kg) significantly (P < 0.05) reduced the kidney choline concentration by 40% and 30% respectively; both hemicholiniums raised the lung choline concentration by about 35%. Only TPHC‐3 caused a significant rise (40%) in liver choline. The choline concentrations in other tissues were unaffected by the hemicholiniums.
THE EFFECTS OF MORPHINE ON THE ACCUMULATION OF HOMOVANILLIC AND 5‐HYDROXYINDOLEACETIC ACIDS IN THE CHOROID PLEXUS OF RATS
Authors: HUANG JEN‐TZAW , WAJDA ISABEL J.
Published: July 2012

1 Choroid plexus obtained from the lateral ventricles of the rat actively accumulated homovanillic acid (HVA) and 5‐hydroxyindoleacetic acid (5‐HIAA).

2 Morphine 5 × 10−6 M to 5 × 10−4 M potentiated 5‐HIAA accumulation but did not affect HVA accumulation. Levorphanol and dextrorphan had little effect.

3 Naloxone at high concentrations inhibited both HVA and 5‐HIAA accumulation.

4 Glutamic acid, glycine, and arginine also decreased 5‐HIAA accumulation, but lysine, tryptophan, and aspartic acid had no effect.

5 Probenecid, naloxone, arginine, glycine, and tryptophan blocked the increase of 5‐HIAA accumulation induced by morphine.

6 Acute or chronic morphine treatment did not increase the accumulation of 5‐HIAA.

7 These results suggest that the increase of 5‐HIAA or HVA in brain by morphine is not due to the inhibition of the elimination of these metabolites from the choroid plexus.
EFFECTS OF GUANETHIDINE ON HISTAMINE RELEASE DURING REFLEX VASODILATATION IN THE DOG
Authors: CONDORELLI M. , RASETTI G. , RENGO F. , RICCIARDELLI B. , SACCÀ L. , TRIMARCO B. , VOLPE M.
Published: July 2012

1 The effects of guanethidine pretreatment on the release of [14C]‐histamine during the reflex vasodilatation induced in the atropinized gracilis muscle by rapid intravenous administration of noradrenaline, were studied in dogs.

2 After guanethidine treatment the haemodynamic reflex response was completely abolished and no appreciable modification of [14C]‐histamine release from the gracilis muscle following intravenous noradrenaline was observed.

3 These results suggest the hypothesis that the withdrawal of the sympathetic discharge represents the mechanism of histamine release during the reflex vasodilatation. Therefore, guanethidine would suppress both the passive and the histaminergic component of the baroreceptor reflex through the abolition of the sympathetic tone.
COMPARATIVE EFFECTS OF HYPOPHYSECTOMY AND ADRENALECTOMY UPON PLASMA AND ADRENAL MONOAMINES IN PREGNANT AND NON‐PREGNANT RATS
Authors: ISMAHAN G. , PARVEZ H. , PARVEZ S. , YOUDIM M.B.H.
Published: July 2012

1 The influence of hypophysectomy and adrenalectomy upon release and storage of adrenaline and noradrenaline during rat oestrous cycle and pregnancy has been studied.

2 Hypophysectomy during the pro‐oestrous phase of the oestrous cycle increased plasma noradrenaline concentration which was unchanged, however, by similar treatment in pregnant females. After adrenalectomy during dioestrous and pro‐oestrous phases, as well as on day 15 post‐coitum, plasma noradrenaline showed an increase, although the increase in pregnant females was greater.

3 Adrenocorticotrophic hormone (ACTH) administration to non‐pregnant and pregnant females increased plasma adrenaline values significantly, compared with control values. Treatment of adrenalectomized rats with hydrocortisone lowered plasma noradrenaline to control values in both non‐pregnant and pregnant females.

4 Hypophysectomy produced a decrease in plasma adrenaline content, whilst ACTH treatment increased it. Plasma adrenaline disappeared completely after adrenalectomy, during the pro‐oestrous phase and pregnancy, but extirpation of adrenals during the dioestrous phase still left appreciable amounts of adrenaline in plasma. Hydrocortisone treatment of both non‐pregnant and pregnant adrenalectomized females resulted in the reappearance of plasma adrenaline

5 Adrenal stores of adrenaline and noradrenaline declined after hypophysectomy but the decreases were greater in pregnant females.

6 Compensatory administration of ACTH to hypophysectomized females increased adrenaline and noradrenaline content of adrenals to control non‐pregnant female values during the pro‐oestrous phase of the oestrous cycle but similar treatment in pregnant females resulted in an increase in adrenaline.

7 Although ACTH administration increased adrenal noradrenaline levels in pregnant hypophysectomized females, the mean value remained below that of non‐operated pregnant females.

8 The results suggest that, during oestrous cycle and pregnancy the effects of pituitary and adrenal hormonal deficiency upon storage and release of monoamines differ quantitatively.
ANORECTIC ACTIVITY OF PROSTAGLANDIN PRECURSORS
Authors: DOGGETT N.S. , JAWAHARLAL K.
Published: July 2012

1 Intraperitoneal and intragastric (i.g.) administration of prostaglandin precursors arachidonic (2 mg, 15 mg/kg, i.p.; 30 mg/kg, i.g.), linolenic (100 mg/kg, i.p.; 200 mg/kg, i.g.) and linoleic (15, 100 mg/kg, i.p.; 100 mg/kg, i.g.) acids to 22 h food‐deprived rats inhibits food intake.

2 This anorexia is similar to that induced by prostaglandin F2α (1 mg/kg, i.p.).

3 At anorectic doses these fatty acids do not cause pyrexia, in fact arachidonic acid causes hypothermia.

4 Prior treatment with indomethacin (15 mg/kg) and paracetamol (50 mg/kg) specifically reverses the anorexia and the behavioural satiety induced by the three fatty acids, while not affecting prostaglandin F2α‐induced suppression of food intake.

5 Results of the present experiments suggest that both physiological and pharmacological modification of appetite could be brought about through an effect on prostaglandin generating systems.