bluuebunny/crossref_metadata_2025 huggingface dataset:
ENKEPHALINS AND DORSAL HORN NEURONES OF THE CAT: EFFECTS ON RESPONSES TO NOXIOUS AND INNOCUOUS SKIN STIMULI
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 methionine enkephalin and methionine enkephalin amide on the responses of neurones of spinal laminae IV and V to noxious and innocuous skin stimuli. The enkephalins were ejected from micropipettes either in the region of cell bodies or in the substantia gelatinosa.

Administered near cell bodies the enkephalins reduced spontaneous firing and cell responses to both types of skin stimuli. These effects were antagonized by naloxone when administered near cell bodies but not when given intravenously in doses (0.3‐0.6 mg/kg) more than adequate to antagonize analgesic doses of morphine.

Administered in the substantia gelatinosa the enkephalins were more selective in their action. The predominant effect was a reduction in nociceptive responses with little effect on non‐nociceptive responses although spontaneous firing was commonly reduced. Naloxone administered either in the substantia gelatinosa or intravenously (0.1‐0.3 mg/kg) reversed these effects of the enkephalins.
SOME EFFECTS OF PROSTAGLANDINS E1 AND E2 AND OF ENDOTOXIN INJECTED INTO THE HYPOTHALAMUS OF YOUNG CHICKS: DISSOCIATION BETWEEN ENDOTOXIN FEVER AND THE EFFECTS OF PROSTAGLANDINS
Authors: ARTUNKAL AKGÜL A. , MARLEY E. , STEPHENSON J.D.
Published: July 2012

Prostaglandins E1 and E2 elevated body temperature of young chicks when injected into the hypothalamus at thermoneutrality (31°C). In contrast, they lowered body temperature when so injected below thermoneutrality (16°C): the relation of the fall in body temperature to increased heat loss and decreased heat production was examined.

The above effects below thermoneutrality were potentiated by pretreatment with inhibitors of prostaglandin synthetase and possible reasons for this potentiation are given.

The ‘O’‐somatic antigen of Shigella dysenteriae consistently evoked hyperthermia when injected into the hypothalamus, irrespective of whether the chicks were within or below thermoneutrality.

Pretreatment with prostaglandin synthetase inhibitors failed to prevent the onset of endotoxin fever; however, duration of the fever, induced by intrahypothalamic injection of the O‐somatic antigen of Shigella dysenteriae was reduced.

The intrahypothalamic injection, below thermoneutrality of prostaglandins E1, E2, noradrenaline, 5‐hydroxytryptamine or carbachol reversed endotoxin fever, inducing even substantial falls in body temperature.

While the results cast some doubts on the role of prostaglandins of the E series as mediators of endotoxin fever in chicks, they cannot be eliminated as mediators until the significance of the reduction in duration of the pyrexic response by indomethacin and 5,8,11,14‐eicosatetraynoic acid, and the degree of synthesis inhibition attained, are known.
PHARMACOLOGICAL AND CERTAIN CHEMICAL PROPERTIES OF AH 10407, AN UNUSUALLY SHORT‐ACTING, COMPETITIVE NEUROMUSCULAR BLOCKING DRUG, AND SOME RELATED COMPOUNDS
Authors: BRITTAIN R.T. , JACK D. , TYERS M.B.
Published: July 2012

1,1′‐Azobis[3‐methyl‐2‐phenylbenzimidazolinium]dimethanesulphonate(AH 10407) has an ultrashort, competitive neuromuscular blocking action in the mouse, cat, dog, Cynamolgus monkey and cotton‐eared marmoset.

AH 10407 is chemically unstable in bicarbonate‐containing solutions and is degraded to inactive products. The half‐life of AH 10407 in vitro in dog and human whole blood and in Krebs physiological solution is about 1.0 minute. In distilled water and in HCO3‐deficient Krebs solution AH 10407 is much more stable. Base catalyzed degradation is shown to be the prime determinant of the duration of action of the drug.

Some pharmacological properties of AH 11244 and AH 11056, close analogues of AH 10407, are briefly described and the duration of their neuromuscular blocking actions rationalized by reference to their chemical stabilities.
THE ENHANCEMENT OF CHLORPROMAZINE‐INDUCED HYPOTHERMIA BY LESIONS IN THE ANTERIOR HYPOTHALAMUS
Authors: CHAI C.Y. , LIN M.T.
Published: July 2012

Administration of chlorpromazine (Cpz), either systemically or centrally, to unanaesthetized rats at an environmental temperature of 23 °C caused dose‐dependent hypothermia.

In order to achieve equivalent hypothermia, intraventricular administration required a total dose of 20 μg Cpz and intraperitoneal administration a dose of 9.7 mg/kg body weight. Accordingly, the dose‐ratio between intraventricular and intraperitoneal administration was 1 to 110. Cpz apparently exerts its hypothermic effect by acting directly on central nervous structures rather than through peripheral sites.

Cpz‐induced hypothermia was potentiated by preoptic anterior hypothalamic (POAH) lesions but not by lesions of the ventromedial nucleus (VMN) of the hypothalamus. It was found that Cpz induced hypothermia most readily in rats with large POAH lesions (‐10.4°C), less so in rats with spinal lesions (‐ 5.5°C) at least with control rats (‐ 2.9°C).
COMPARATIVE INHIBITORY EFFECTS OF 3‐QUINUCLIDINYL BENZILATE (QNB) AND ATROPINE ON AMYLASE RELEASE FROM RAT PANCREAS
Authors: MORISSET J. , NG K.H. , POIRIER G.G.
Published: July 2012

Secretion of amylase from rat pancreas stimulated by urecholine was studied in relation to its inhibition by atropine and 3‐quinuclidinyl benzilate (QNB).

Urecholine‐induced secretion was completely abolished by atropine at 10−6 M and QNB at 10−8 M. Significant inhibition could be detected at 10−8 M atropine and 10−10 M QNB.

The secretory response to pancreozymin was not blocked either by atropine or QNB.

The inhibitory effect of QNB remained for at least 90 min after its removal from the incubation medium.

It is concluded that QNB is 10 times more potent than atropine in inhibiting pancreatic amylase secretion induced by urecholine.
THE CARDIOVASCULAR RESPONSE TO DIMAPRIT, A SELECTIVE HISTAMINE H2‐RECEPTOR AGONIST
Authors: FLYNN SHEILA B. , JOHNSTON BARBARA M. , OWEN D.A.A.
Published: July 2012

The cardiovascular responses to dimaprit (S‐(3‐dimethylaminopropyl) isothiourea), a selective histamine H2‐receptor agonist have been studied in anaesthetized cats, dogs, rats and rabbits.

Dimaprit lowered systemic arterial blood pressure in all species whether given by intravenous injection or by continuous infusion. Intra‐arterial injections or infusions caused vasodilatation in the femoral vascular bed.

In the cat, continuous intravenous infusions of dimaprit lowered blood pressure without any significant change in heart rate or cardiac output. The fall in blood pressure was thus due to a decrease in peripheral vascular resistance.

Dimaprit, given intravenously, increased coronary and gastric blood flows and there were associated marked reductions in vascular resistance. Small reductions in vascular resistance occurred in skeletal muscle, in the intestine and the kidneys.

The histamine H2‐receptor antagonists, metiamide and cimetidine, antagonized the depressor and vasodilator responses to dimaprit.
EFFECTS OF N‐BENZYL‐ L‐VALINE ON CONTRACTIONS OF GUINEA‐PIG MYOMETRIUM in vitro
Authors: PICKLES V.R.
Published: July 2012

A claim that N‐benzylvaline is an exceedingly potent stimulant of guinea‐pig myometrium has not been confirmed, but less potent stimulant or inhibitory effects were seen in a few experiments.
β‐ADRENOCEPTOR STIMULATION OF EXOCRINE SECRETION FROM THE RAT PANCREAS
Authors: FURUTA Y. , HASHIMOTO K. , WASHIZAKI M.
Published: July 2012

Effects of catecholamines given intravenously on exocrine secretion from the pancreas were investigated in anaesthetized rats. The flow rate of pancreatic juice under resting conditions was 11.1 ± 3.2 μl per hour in 100 animals.

Dopamine (0.3–3 mg/kg) and isoprenaline (1–10 μg/kg) induced almost the same increase in the pancreatic secretion, so that dopamine was 300 times less potent than isoprenaline. The relative potency of the two amines for stimulation of pancreatic secretion was equivalent to that for β‐stimulation of the contractile force of the left ventricle in vivo.

Propranolol (0.5 mg/kg) antagonized completely the dopamine‐ and isoprenaline‐induced stimulation of the pancreatic secretion.

Haloperidol (10 mg/kg) failed to suppress the secretory effect of dopamine on the exocrine pancreas but abolished the dopamine‐induced hypotension.

The dopamine‐induced secretion was not modified by atropine (3 mg/kg), phenoxybenzamine (3 mg/kg), vagotomy or pithing.

Adrenaline and noradrenaline (10 μg/kg) induced secretion after phenoxybenzamine treatment (3 mg/kg).

It is suggested that the rat pancreas has a stimulatory β‐adrenoceptor mechanism of exocrine secretion.
VASOPRESSIN RELEASE PRODUCED IN ANAESTHETIZED CATS BY ANTAGONISTS OF γ‐AMINOBUTYRIC ACID AND GLYCINE
Authors: FELDBERG W. , E SILVA M. ROCHA
Published: July 2012

In cats anaesthetized with chloralose, the central excitatory substances, tubocurarine, picrotoxin, bicuculline, leptazol and strychnine, were applied to the exposed ventral surface of the brain stem through paired Perspex rings placed across the medulla and their effects on vasopressin release and arterial blood pressure were examined.

The excitatory substances released large amounts of vasopressin when applied to an area 6–9 mm caudal to the trapezoid bodies. From this area vasopressin release was previously obtained with nicotine.

With nicotine, the vasopressin release occurred almost instantaneously and tachyphylaxis developed rapidly. With the excitatory substances the release increased gradually and there was no tachyphylaxis. When these substances were applied for several minutes, the release reached its maximum a considerable time after their removal, except with leptazol when release diminished at once after removal.

The excitatory substances had little or no effect on arterial blood pressure when applied to the vasopressin releasing area, but produced strong pressor responses when applied to a more rostrally situated area.

It is concluded that the excitatory substances release vasopressin and raise arterial blood pressure because they are antagonists of γ‐aminobutyric acid and/or glycine and that numerous inhibitory neurones which release these amino‐acids synapse at the ventral surface of the medulla. The physiological function of those which synapse at the vasopressin releasing area may be to act as a brake on vasopressin release, and of those which synapse at the more rostrally situated area to act as a brake on arterial blood pressure.
EFFECTS OF Δ‐TRANS‐TETRAHYDROCANNABINOL ON MECHANICAL PERFORMANCE OF ISOLATED HEART MUSCLE PREPARATIONS
Authors: GRAHAM J.D.P. , GREY A.C. , HENDERSON A.H. , LEWIS M.J.
Published: July 2012

The effects of four concentrations of Δ1‐trans‐tetrahydrocannabinol (Δ1‐THC) (0.1, 1, 5 and 20 μg/ml) were compared to that of the vehicle (ethanol, 0.5 μl/ml) on the mechanical performance of isolated cardiac muscle of the cat and rat.

In rat isolated papillary muscles, Δ1‐THC (20 μg/ml) caused a decline in mechanical performance (−8% in developed tension and −11% in Vmax) in contrast to the apparent lack of effect of ethanol.

All other parameters of mechanical performance studied in both rat and cat papillary muscles were unaffected by Δ1‐THC when compared with ethanol.

It was concluded that Δ1‐THC in concentrations up to 20 μg/ml had negligible effect on contractile performance, the time course of contraction or muscle elasticity in rat and cat isolated papillary muscle preparations under the conditions studied.
CATECHOLAMINE UPTAKE BY ISOLATED CORONARY ARTERIES AND ATRIA OF THE KITTEN
Authors: CORNISH E.J. , GOLDIE R.G. , MILLER R.C.
Published: July 2012

Kitten coronary arteries and atria incubated with [3H]‐(‐)‐noradrenaline or [3H]‐(±)‐isoprenaline showed concentration‐ and temperature‐dependent accumulation of amines (unchanged and/or as metabolites). In addition, coronary arteries incubated with [3H]‐(+)‐isoprenaline showed temperature‐insensitive amine accumulation due to binding to connective tissue fibres.

With low concentrations of [3H]‐(‐)‐noradrenaline (20 ng/ml) accumulation of radioactivity in both tissues was neuronal since it was reduced by desipramine, metaraminol or cocaine but not by the extraneuronal inhibitor, cortisol.

In coronary arteries incubated with [3H]‐(±)‐isoprenaline (5 jig/ml) for 1 or 10 min, uptake was extraneuronal since it was inhibited by cortisol, 17, B‐oestradiol or phenoxybenzamine.

Atria incubated with (±)‐isoprenaline (5 to 1000 jig/ml) showed non‐neuronal, biphasic accumulation of amine. There was a high capacity, low affinity initial uptake process (apparent Km 136 gM) which was resistant to steroidal extraneuronal uptake inhibitors but which could be abolished by phenoxybenzamine. A slower uptake occurred after 2 min which was sensitive to steroidal and other extraneuronal uptake inhibitors.

Inhibition of uptake processes did not alter sensitivity of coronary arteries to dilator effects of catecholamines. However, experiments with extraneuronal uptake inhibitors were limited by the relaxant effects of cortisol and 17f3‐oestradiol themselves.

In atria inhibition of neuronal uptake by desipramine or cocaine led to super‐sensitivityto (‐)‐noradrenaline but not to (‐)‐adrenaline or (±)‐isoprenaline. Chronotropic responses to (‐)‐noradrenaline were increased five fold and inotropic responses three fold.

Inhibition of extraneuronal uptake led to selective super‐sensitivityto (±)‐isoprenaline. Cortisol increased chronotropic responses ten fold and inotropic responses three fold, while 17f‐oestradiol produced less than two fold increases in sensitivity to isoprenaline.
ENHANCEMENT BY AN ANTAGONIST OF TRANSMITTER RELEASE FROM FROG MOTOR NERVE TERMINALS
Authors: SILINSKY E.M.
Published: July 2012

The effect of Ba2+ on the synchronous release of acetylcholine from frog motor nerve terminals was studied by conventional electrophysiological techniques.

When Ca2+ and Ba2+ were the only divalent cations in the bathing fluid, Ba2+ caused a presynaptic reduction in the amplitude of the endplate potential (e.p.p.). This effect was surmountable by increasing the Ca2+ concentration.

The affinity constant (KA) for Ba2+, calculated on the assumption that Ba2+ is a competitive inhibitor of the agonist, Ca2+, was 1.1 + 0.4 mM−1 (mean + s.e.mean, n = 8).

When e.p.ps were depressed by the addition of 1 mm Mg2+, addition of Ba2+ (1 to 3 mm) caused either a further presynaptic depression of moderate magnitude or had no additional effect.

When e.p.p.s were depressed with [Mg2+] > 2 mm, addition of Ba2+ > 0.9 mm enhanced the e.p.p. amplitude by a presynaptic mechanism.

The interaction of the divalent cation antagonists Mg2+ and Ba2+ with the agonist, Ca2+ is discussed. It is demonstrated that a model which considers the nonequilibrium, kinetic properties of binding can be used to describe interactions between divalent cations at the external surface of the motor nerve ending.
EFFECTS OF γ‐AMINOBUTYRIC ACID ON NERVE TERMINAL EXCITABILITY IN A SLICE PREPARATION OF CUNEATE NUCLEUS
Authors: HAYES ANN G. , SIMMONDS M.A.
Published: July 2012

Superfusion of a slice preparation of the rat cuneate nucleus with γ‐aminobutyric acid (GABA) depolarized the afferent nerve fibres and increased their excitability. However, before the depolarization had reached its peak the increased excitability reversed to a decreased excitability, an effect which outlasted the depolarization.

Both components of the GABA excitability response were dose‐related, CI “‐dependent and antagonized by bicuculline.

Possible mechanisms underlying the sequence of excitability changes are discussed.
PLASMA CLEARANCE OF NEOSTIGMINE AND PYRIDOSTIGMINE IN THE DOG
Authors: BAKER P.R. , CALVEY T.N. , CHAN K. , MACNEE C.M. , TAYLOR K.
Published: July 2012

The pharmacokinetics of neostigmine and pyridostigmine was studied in conscious dogs by the use of a cross‐over design.

Both neostigmine and pyridostigmine were cleared from plasma in a biexponential manner.

The apparent volume of distribution of pyridostigmine was invariably greater than that of neostigmine, and its fast disposition half‐life was approximately three times longer.

The whole body clearance and the urinary elimination of pyridostigmine was approximately twice that of neostigmine.

The slow disposition half‐life of pyridostigmine was approximately three times longer than that of neostigmine, suggesting that the longer duration of action of pyridostigmine is related to the differential clearance of the two quaternary amines from plasma.
EFFECTS OF CHOUNOCEPTOR ANTAGONISTS ON THE SUCKLING‐INDUCED AND EXPERIMENTALLY EVOKED RELEASE OF OXYTOCIN
Authors: CLARKE G. , FALL CAROLINE H.D. , LINCOLN D.W. , MERRICK LYNDA P.
Published: July 2012

In the anaesthetized lactating rat, the suckling of the young causes the regular release (about every 7 min) of brief pulses of oxytocin (0.5 to 1.0 mu), which each produce a single transient increase in intramammary pressure.

The effects of several cholinoceptor antagonists were studied in relation to this natural reflex, and also the release of oxytocin evoked by the intraventricular injection of cholinomimetics.

Reflex milk ejection was blocked by the nicotinic antagonists mecamylamine and hexamethonium, and the inhibition was dose‐dependent (ED50 of 1 mg/kg i.v. and 5 mg/kg i.v., respectively). Despite the use of high doses, the muscarinic antagonists atropine (200 mg/kg), hyoscine (90 mg/kg) and benzhexol (30 mg/kg) all failed to prevent the reflex release of oxytocin.

Acetylcholine (20 to 100 ug), bethanechol (0.2 to 4.0 ug) and carbachol (0.01 to 0.2 ug) injected into the cerebral ventricals stimulated a sustained release of oxytocin, which produced multiple increases in intramammary pressure. Nicotine (200 ug) was relatively ineffective by this route.

The release of oxytocin by intraventricular bethanechol or carbachol was abolished by atropine (0.1 to 1.0 mg/kg) but not by mecamylamine (5 mg/kg) or hexamethonium (5 mg/kg).

None of the antagonists used significantly affected either the release of oxytocin following electrical stimulation of the neurohypophysis or the mammary sensitivity to endogenous or exogenous oxytocin.

The results suggest that the neural pathway controlling the reflex release of oxytocin during suckling in the rat contains a cholinergic component, which acts through nicotinic receptors. A second cholinergic pathway, of the muscarinic type, may also exist. The role of these two pathways is discussed.
THE BINDING OF HALOPERIDOL TO HUMAN BLOOD PLATELETS AND INTERACTIONS WITH 5‐HYDROXYTRYPTAMINE AND DOPAMINE
Authors: BOULLIN D.J. , MOLYNEUX D. , ROACH B.
Published: July 2012

The binding of [3H]‐5‐hydroxytryptamine ([3H]‐5‐HT), [3H]‐haloperidol and [3H]‐dopamine to human blood platelets was investigated and the effects of unlabelled haloperidol on [3H]‐5‐HT binding and (+)‐ and (—)‐butaclamol on [3H]‐haloperidol were studied.

Scatchard analysis did not show any specific binding of [3H]‐haloperidol or [3H]‐dopamine to platelets, but two binding sites were identified for binding of [3H]‐5‐HT.

Unlabelled haloperidol reduced the binding of 5‐HT in concentrations comparable to those inhibiting 5‐HT‐induced platelet aggregation; (+)‐ and (‐)‐butaclamol did not affect the binding of [3H]‐haloperidol.

It is concluded that haloperidol binding represents saturation of the platelet membrane, and that the platelet is not a suitable model for investigation of dopamine‐drug interactions.
THE EFFECTS OF PENTOBARBITONE AND URETHANE ON PULMONARY AIRWAY RESISTANCE IN GUINEA‐PIGS AND THEIR INTERACTIONS WITH DRUGS
Authors: ADVENIER C. , BOISSIER J.R. , HO S. , MALLARD B. , RUFF F.
Published: July 2012

Propranolol increased pulmonary airway resistance (PAR) in the conscious guinea‐pig, whereas atropine had no effect, suggesting the existence of a continual sympathetic bronchodilator tone.

The direct bronchoconstrictor effects of histamine, acetylcholine and 5‐hydroxytryptamine were modified by autonomic reflexes: a bronchodilator one, abolished by propranolol, and a cholinergic bronchoconstrictor one, seen with histamine.

Pentobarbitone increased PAR, an effect which was reduced by propranolol but which was unaffected by atropine. The bronchoconstrictor effects of histamine, acetylcholine and 5‐hydroxytryptamine were potentiated by pentobarbitone.

Pentobarbitone therefore appears to inhibit the adrenergic bronchodilator tone and to depress adrenergic reflexes, these being the preponderant autonomic influences in these experiments.

Like pentobarbitone, urethane increased PAR in the conscious guinea‐pig and potentiated the bronchoconstrictor effects of the three amines. These actions are similarly attributed to a reduction in adrenergic influences.
THE PROTECTIVE EFFECT OF SOME PHENOTHIAZINE DERIVATIVES AGAINST STREPTOLYSIN O
Authors: BESLUAU D. , GAUTHIER‐RAHMAN S. , HALPERN B.
Published: July 2012

Chlorpromazine (Cpz) and promethazine (Pmz) protected mice against lethal doses of streptolysin O (SLO) given intravenously. Three other phenothiazine derivatives had similar but lesser effects.

The protective effect developed slowly; maximal protection was obtained 4 h after subcutaneous injection of Cpz and Pmz.

The haemolytic activity of SLO in vitro was also inhibited by Cpz.
COMPARATIVE STUDIES ON IMMUNOLOGICALLY AND NON‐IMMUNOLOGICALLY PRODUCED SLOW‐REACTING SUBSTANCES FROM MAN, GUINEA‐PIG AND RAT
Authors: MORRIS H.R. , PIPER PRISCILLA J. , TAYLOR G.W. , TIPPINS J.R.
Published: July 2012

Slow‐reacting substance of anaphylaxis (SRS‐A) was produced by antigen challenge of passively sensitized human lung and actively sensitized guinea‐pig lung.

A slow‐reacting substance (SRS) was prepared from the peritoneal fluid of rats treated with calcium ionophore A23187.

These substances were extensively purified by charcoal adsorption, Sephadex G‐15 gel filtration, ether extraction and reverse phase high pressure liquid chromatography.

The three substances are pharmacologically, chemically and chromatographically indistinguishable.

Our data suggest that the same SRS entities are released from a variety of tissues and that these acidic lipids may have a wider physiological significance than just anaphylaxis.
EFFECTS OF THE VENOM OF THE GREEN MAMBA, Dendroaspis angusticeps ON SKELETAL MUSCLE AND NEUROMUSCULAR TRANSMISSION
Authors: BARRETT J.C. , HARVEY A.L.
Published: July 2012

The venom of the green mamba, Dendroaspis angusticeps, was tested for effects on neuromuscular transmission and skeletal muscle contractility in isolated phrenic nerve‐hemidiaphragm preparations of the rat and mouse, chick biventer cervicis muscle preparations and in aneural cultures of embryonic chick skeletal muscle.

The venom (10 to 40 μg/ml) augmented the responses to indirect but not direct stimulation. As the venom did not have anticholinesterase activity and did not increase receptor sensitivity, it is likely that the venom enhanced release of acetylcholine.

Higher concentrations of venom (40 to 80 μg/ml) inhibited acetylcholine receptor sensitivity.

Prolonged exposure to the higher concentrations of venom produced a failure of muscle contractility. Signs of muscle degeneration were seen in skeletal muscle cultures.
THE FAILURE OF INDOMETHACIN TO ALTER ACTH‐INDUCED ADRENAL HYPERAEMIA OR STEROIDOGENESIS IN THE ANAESTHETIZED DOG
Authors: GERBER JOHN G. , NIES ALAN S.
Published: July 2012

The response of adrenal blood flow to adrenocorticotropic hormone (ACTH) was measured with radioactive microspheres in anaesthetized, dexamethasone‐treated, mongrel dogs.

Adrenocorticotropic hormone (2 u/h i.v.) increased adrenal blood flow within 15 min and this persisted for the duration of the infusion.

Cortisol concentrations also rose with ACTH infusion.

Indomethacin (6 mg/kg i.v. followed by 1 mg/min) did not affect the adrenal response to ACTH although plasma concentrations of indomethacin (21.9 ± 2.5 μg/ml) adequate to suppress prostaglandin synthesis were achieved.

We conclude that prostaglandins are not required for steroidogenesis or the adrenal haemodynamic response to ACTH.
THE EFFECTS OF INERT GASES AND OTHER GENERAL ANAESTHETICS ON THE RELEASE OF ACETYLCHOLINE FROM THE GUINEA‐PIG ILEUM
Authors: HALLIDAY D.J.X. , LITTLE HILARY J. , PATON W.D.M.
Published: July 2012

The actions of a range of general anaesthetic agents on the rates of release of acetylcholine from the guinea‐pig ileum were tested, by means of a superfusion system designed to maintain the tissues under physiological conditions in a high pressure chamber.

Anaesthetic pressures of nitrous oxide, nitrogen, argon, sulphur hexafluoride and carbon tetra‐fluoride caused increases in acetylcholine ouput but the concentrations required did not parallel their general anaesthetic potencies. The changes were not altered by the application of a pressure of helium which reverses their general anaesthetic actions in vivo.

Urethane (50.5 mm and 101 mm, but not 16.8 mm) decreased acetylcholine release rates and this effect was not reversed by helium pressure.

Octanol (1.0 mm, but not 0.124 mm or 0.496 mm) decreased the acetylcholine output. This action was not reversed by helium pressure. The lack of effect on acetylcholine release from tetrodotoxin‐treated tissues suggested that the changes were produced by blockade of action potential conduction.

Phenobarbitone (0.4 mm but not 0.2 mm) also decreased acetylcholine output. Although the concentrations required were lower than those which have been previously shown to block axonal conduction, no changes were seen in tetrodotoxin‐treated tissues. The decreases were less when helium pressure was applied than at atmospheric pressure but full pressure reversal, as occurs in vivo, was not seen.

The effects on acetylcholine output exerted by the anaesthetics studied did not reflect their general anaesthetic action in the concentrations required, the direction of the changes produced or in the response to helium pressure. They represent specific actions which are likely to contribute to the individual differences which are seen between the physiological actions of the anaesthetics in vivo.
INHIBITION BY PENTOBARBITONE AND URETHANE OF THE in vitro RESPONSE OF THE ADENOHYPOPHYSIS TO LUTEINISING HORMONE‐RELEASING HORMONE IN MALE RATS
Authors: CARTER D.A. , DYER R.G.
Published: July 2012

The effect of urethane (ethyl carbamate) and sodium pentobarbitone on the luteinising hormone‐releasing hormone (LH—RH)‐stimulated secretion of luteinising hormone (LH) was investigated with hemipituitaries obtained from male rats and incubated in vitro.

Urethane and pentobarbitone were added to the incubation medium to provide final concentrations of 2.2 mg or 4 μg/ml and 100 μg or 0.1 μg/ml respectively. The high doses of these anaesthetics blocked the LH—RH stimulated secretion of LH. The low doses significantly reduced the amounts of LH released in response to LH—RH but did not block the response completely.

Both concentrations of urethane reduced the basal release of LH.

The inhibitory action of the anaesthetics was reversible.

The results indicate that the two anaesthetics most commonly used in neuroendocrine experiments have a significant inhibitory action on the release of LH from the adenohypophysis.
RELAXATION OF GUINEA‐PIG FUNDIC STRIP BY ADENOSINE, ADENOSINE TRIPHOSPHATE AND ELECTRICAL STIMULATION: LACK OF ANTAGONISM BY THEOPHYLLINE OR ATP TREATMENT
Authors: BAER HANS P. , FREW ROBERT
Published: July 2012

Theophylline relaxed isolated strips of guinea‐pig stomach fundus in a dose‐dependent manner; above 50 to 100 μm responses showed no fade for up to 90 min.

Relaxant responses to adenosine, adenosine triphosphate (ATP), noradrenaline, and to electric field stimulation of non‐adrenergic inhibitory nerves were not affected in a significant manner in the presence of 50 μm theophylline.

In tissues which showed complete fade of initial responses in the continued presence of 50 μm ATP, the effects of stimulation of non‐adrenergic inhibitory nerves remained unaltered, suggesting that the ATP receptor has no function in non‐adrenergic inhibitory transmission in this tissue.

These findings are opposite to those of Okwuasaba, Hamilton & Cook (1977), who claimed that 50 μm theophylline almost fully inhibited relaxation induced by adenosine, ATP and nerve stimulation and that ATP‐induced fade also abolished sensitivity to inhibitory nerve stimulation.
INCORPORATION AND METABOLISM OF [14C]‐ARACHIDONIC ACID IN GUINEA‐PIG LUNGS
Authors: JOSE P.J. , SEALE J.P.
Published: July 2012

Following infusion of [14C]‐arachidonic acid into guinea‐pig isolated lungs more than half the administered radioactivity was retained by the lung.

The majority of the retained radioactivity was present in the phospholipid fraction with lesser amounts in the neutral lipid and free fatty acid fractions. When fatty acid methyl esters of the phospholipid fraction were prepared, 80% of the radioactivity co‐chromatographed with methyl arachidonate.

Transformation to cyclo‐oxygenase products and subsequent emergence in lung effluent accounted for approximately 20% of infused radioactivity.

After pretreatment of lungs with [14C]‐arachidonic acid, stimulation of arachidonic acid metabolism with injections of partially purified slow‐reacting substance of anaphylaxis (SRS‐A), bradykinin or antigen challenge released rabbit aorta contracting substance (RCS) and prostaglandin‐like substances (PGLS) but little radioactivity. Furthermore, repeated injections of SRS‐A or bradykinin released similar amounts of RCS and PGLS but diminishing amounts of radioactivity.

These data indicated that exogenous arachidonic acid was taken up by the lung and incorporated into phospholipids. However, this newly incorporated arachidonic acid had not equilibrated with the pool activated by SRS‐A, bradykinin and antigen challenge for conversion to cyclo‐oxygenase products.
PROSTAGLANDINS AND THE CONTRACTILE ACTION OF BRADY‐KININ ON THE LONGITUDINAL MUSCLE OF RAT ISOLATED ILEUM
Authors: WALKER R. , WILSON KEITH A.
Published: July 2012

The effect of the prostaglandin synthesis inhibitors aspirin and indomethacin (Ind) was investigated upon contractions of the perfused isolated terminal ileum of the rat to bradykinin (Bk) or potassium chloride (KC1). The release of a prostaglandin‐like substance (PGLS) from the ileum was simultaneously assayed on the rat fundus strip (RFS).

Aspirin (610 μm) or Ind (28 μm) reduced contractions of the ileum to Bk perfused over the mucosal surface but not to Bk perfused over the serosal surface.

After perfusion of either ileal surface the effluent potentiated the contractions of the RFS to Bk. No potentiation was observed in the presence of either Ind or aspirin.

Contractions of the RFS to Bk were potentiated by prostaglandin E2 (PGE2) (0.7 × 10−12 m and 1.4 × 10−12 m) but not by either a higher (2.8 × 10−12 m) or a lower (0.35 × 10−12 m) concentration of PGE2. No potentiation was observed with prostaglandin F2α (PGF2α) at the concentrations studied.

Only the contractile action of Bk acting on the mucosal surface of the rat isolated perfused ileum seems to involve prostaglandin synthesis.
SELECTIVE ANTAGONISM BY BENZODIAZEPINES OF NEURONAL RESPONSES TO EXCITATORY AMINO ACIDS IN THE CEREBRAL CORTEX
Authors: ASSUMPÇÃO J.A. , BERNARDI N. , BROWN J. , STONE T.W.
Published: July 2012

The recently discovered benzodiazepine receptor exists in high concentration in the cerebral cortex. We have, therefore, examined the effects of diazepam and chlordiazepoxide on cortical neurone responses to excitatory and inhibitory amino acids and acetylcholine, in the cortex of rats anaesthetized with urethane.

Chlordiazepoxide applied by microiontophoresis reduced the responses to glutamate and aspartate but acetylcholine responses were unaffected on most cells even by much higher doses of benzodiazepine. γ‐Aminobutyric acid (GABA) and taurine responses were unaffected on most cells, but were reduced on 4 of 25 units. After intravenous diazepam, responses to GABA and taurine were reduced on 3 cells and unchanged on 11.

On Purkinje cells in the cerebellum a number of cells (5 of 16) exhibited a substantial increase in responses to GABA and taurine following intravenous or iontophoretic application of benzodiazepines.

It is suggested that the highly selective reduction of excitatory amino acid responses in the cerebral cortex may be of particular relevance to the behavioural effects of benzodiazepines.
PHARMACOLOGICAL EFFECTS OF PHOSPHATIDYLSERINE LIPOSOMES: THE ROLE OF LYSOPHOSPHATIDYLSERINE
Authors: BIGON E. , BOARATO E. , BRUNI A. , LEON A. , TOFFANO G.
Published: July 2012

Unique among the phospholipids, phosphatidylserine depresses brain energy metabolism when injected intravenously into mice in the form of sonicated liposomes. The possibility that this effect results from a metabolic transformation of phosphatidylserine is examined in this paper.

A strong enhancement of the phosphatidylserine effect is induced by the incubation of liposomes with rat serum. Similar phosphatidylserine activation is observed after the incubation of the phospholipid with purified phospholipase A2 from pancreas. In both cases phosphatidylserine is split into the deacylated derivative, lysophosphatidylserine.

Lysophosphatidylserine reproduces with greater efficacy the effect of phosphatidylserine on brain energy metabolism. Other lysophospholipids are not effective.

It is concluded that the pharmacological effects of phosphatidylserine liposomes is due to the generation of lysophosphatidylserine.
EFFECTS OF A COMBINED OESTROGEN‐PROGESTIN PREPARATION ON GASTRIC ACID AND PEPSIN SECRETION, SERUM GASTRIN CONCENTRATION AND BILIARY SECRETION OF BILE ACIDS, PHOSPHOLIPIDS, AND CHOLESTEROL IN THE CAT
Authors: HIRST B.H. , LUND P. KAY , REED THE LATE J.D. , SANDERS D.J. , SHAW B. , TAYLOR W.
Published: July 2012

Daily ethinyloestradiol (50μg) and norethisterone acetate (1 mg) treatment (Minovlar) was investigated on gastric acid and pepsin secretion, and fasting serum gastrin concentration in six conscious female cats prepared with chronic gastric fistulae. The effect on biliary secretion of bile acids, phospholipids, and cholesterol was investigated in three conscious female cats prepared with chronic gastric and intestinal fistulae, and cholecystectomy.

Treatment for 49 days did not alter the gastric acid or pepsin response to either intravenous pentagastrin infusions or a food stimulus. The fasting serum gastrin concentration remained unaltered throughout the study.

Treatment for 18 days did not alter the percentage concentration of cholesterol in the bile, but reduced the percentage concentration of phospholipid. This was mirrored by a rise in the percentage concentration of bile acids in the bile. These trends were quickly reversed on cessation of treatment.

There was no sign of cholestasis associated with the treatment. Intestinal flow remained constant throughout the study, there was no lithocholic acid or other abnormal bile acids detectable in any samples, and there was no change in serum aspartate aminotransferase concentration.

The results suggest that in female cats, treatment with a combined oestrogen‐progestin preparation does not exert any beneficial effects on the aetiology of peptic ulceration through the reduction of acid or pepsin secretion, or the lowering of serum gastrin concentration. The preparation shows a tendency to produce more lithogenic bile, and this may partly explain the greater incidence of gall stones in women on the contraceptive pill.
POSSIBLE MECHANISMS OF ACTION OF Gymnodinium breve TOXIN AT THE MAMMALIAN NEUROMUSCULAR JUNCTION
Authors: SHINNICK‐GALLAGHER PATRICIA
Published: July 2012

The mechanism of action of a crude fraction of Gymnodinium breve toxin (GBTX) was investigated by intracellular recording techniques in the rat phrenic nerve diaphragm preparation.

GBTX (2 μg/ml) decreased the input resistance of the muscle membrane concomitantly with a depolarization of the resting membrane potential.

A low sodium solution reversed or prevented a GBTX‐induced membrane depolarization.

Tetrodotoxin (TTX) antagonized a GBTX‐induced increase in miniature endplate potential (m.e.p.p.) frequency and repolarized a GBTX‐depolarized membrane. Pretreatment with TTX prevented GBTX effects.

GBTX reversibly reduced depolarizations produced by bath applied acetylcholine (ACh). The membrane depolarization was not responsible for the depression of ACh responses.

These findings suggest that GBTX increases m.e.p.p. frequency and depolarizes the resting membrane potential by increasing sodium permeability. The reduction of ACh‐induced depolarizations suggests that GBTX may be acting at some site on the ACh receptor.
PHENOBARBITONE INTERACTION WITH ORAL CONTRACEPTIVE STEROIDS IN THE RABBIT AND RAT
Authors: BACK D.J. , BRECKENRIDGE A.M. , CRAWFORD FRANCESCA E. , ORME M.L'E. , ROWE P.H.
Published: July 2012

The effect of phenobarbitone on the single dose pharmacokinetics of the synthetic steroids, ethinyloestradiol (EE2) and norethisterone, has been studied in the rabbit and rat.

EE2 is subject to an extensive first pass effect (96%). The plasma clearance of EE2 approaches total hepatic blood flow. It is suggested that a secondary peak in EE2 plasma concentration time curves at 5 h is due to enterohepatic recycling. Phenobarbitone had no effect on plasma EE2 concentrations following intravenous administration and produced a variable decrease after oral administration.

In phenobarbitone‐treated rabbits, following intravenous administration of norethisterone there was no significant change in the area under the curve (AUC) compared to controls. In contrast, following oral administration of norethisterone to treated rabbits, the AUC was 20% and the peak plasma concentration 17% of that in controls.

The data in rabbits are consistent with drugs which are highly extracted by the liver.

In rats, phenobarbitone had no effect on plasma norethisterone concentrations following intravenous or hepatic portal (bolus) administration, but caused a decrease in systemic availability after both infusion into the portal vein (over a period of 5 min) and oral administration.

It is concluded that the rate of delivery of norethisterone to the liver is important in determining whether or not enzyme induction will cause an increased first pass effect.

Phenobarbitone caused an increase in conjugation of norethisterone in the gastrointestinal tract of rats.
COMPARATIVE STUDY OF THE EFFECTS OF 4‐AMINOPYRIDINE AND TETRAETHYLAMMONIUM ON NEURO‐EFFECTOR TRANSMISSION IN THE GUINEA‐PIG VAS DEFERENS
Authors: ITO YUSHI , KORENAGA SUSUMU , TAJIMA KIKUO
Published: July 2012

Effects of 4‐aminopyridine (4‐AP) and tetraethylammonium (TEA) on the neuro‐effector junction of the guinea‐pig vas deferens were investigated by microelectrode and double sucrose gap techniques.

4‐AP (0.05 to 0.5 mm) or TEA (0.5 to 1 mm) did not alter the membrane potential, or the membrane input resistance of the smooth muscle cell.

The amplitude and frequency of the miniature junction potentials (m.e.j.ps) were not modified by treatment with 4‐AP (0.05 to 0.5 mm) or TEA (1 mm).

4‐AP (1 mm) increased the membrane input resistance, enhanced the spike amplitude of the smooth muscle cells and thereby augmented the amplitude of twitch contraction.

4‐AP (0.05 to 0.5 mm) or TEA (1 mm) markedly increased the amplitude of excitatory junction potentials (e.j.ps), but the facilitation phenomena produced by repetitive stimulation were not affected.

The duration of the extracellularly recorded action potential from the small nerve bundle was prolonged by 4‐AP (0.5 mm).

The amplitude of the e.j.p. was dependent on the external concentration of calcium. A straight line was produced when the amplitude of the e.j.p. and [Ca]o was plotted on a double log scale. Application of 4‐AP resulted in a parallel shift of this line to the left.

These results indicate that 4‐AP (0.05 to 0.5 mm) and TEA (0.5 to 1.0 mm) prolonged the action potential generated from the sympathetic nerve terminal thus enhancing the amplitude of the e.j.p. due to an increase in the Ca‐influx. However, in the concentrations used, these compounds did not modify the Ca‐mobilization in the nerve terminal or the postsynaptic membrane during the resting state.
THE EFFECT OF CONDITIONS INFLUENCING ENDOGENOUS PROSTAGLANDINS ON THE ACTIVITY OF Δ′‐TETRAHYDROCANNABINOL IN MICE
Authors: FAIRBAIRN J.W. , PICKENS JOAN T.
Published: July 2012

The cataleptic effect of Δ′‐tetrahydrocannabinol (THC) depends upon the availability of the precursors of prostaglandins and the response is reduced in mice maintained on a diet deficient in arachidonic acid (AA) and restored by exogenous AA given intraperitoneally, or by feeding a normal diet.

In yeast‐induced fever, which is accompanied by an increase in the synthesis of prostaglandins, THC shows an enhanced cataleptic effect.

Exposure to cold which results in depletion of prostaglandins reduces the effect of THC.
PROSTACYCLIN‐DEPENDENT ACTIVATION OF ADENYLATE CYCLASE IN A NEURONAL SOMATIC CELL HYBRID: PROSTANOID STRUCTURE‐ACTIVITY RELATIONSHIPS
Authors: BLAIR I.A. , HENSBY C.N. , MacDERMOT J.
Published: July 2012

Prostacyclin activates adenylate cyclase of the NCB‐20 neuronal hybrid cell line.

There is a guanosine 5′‐triphosphate requirement for the activation of adenylate cyclase by 5,6β‐dihydroprostacyclin (a stable analogue of prostacyclin).

Steady‐state kinetic analysis of the activation of adenylate cyclase by 5,6β‐dihydroprostacyclin suggests a simple non‐cooperative bimolecular interaction between the ligand and a single receptor population.

Structure‐activity relationships of selected prostanoids elucidated certain functional requirements for activation of adenylate cyclase.
STUDIES ON THE MECHANISM OF ACTION OF VARIOUS VASODILATORS
Authors: GAGNON G. , REGOLI D. , RIOUX F.
Published: July 2012

The vascular relaxant effects of histamine, adenosine, isoprenaline nitroglycerine, papaverine and 3‐isobutyl‐1‐methylxanthine (IBMX) were assessed individually, in strips of rabbit renal artery moderately contracted with noradrenaline (NA) in the absence or presence of phosphodiesterase inhibitors (papaverine and IBMX) or verapamil, a Ca2+ antagonist.

The vasodilator effect of histamine was potentiated by papaverine (6.1 × 10−7 m) and IBMX (4.4 × 10−5 m) but inhibited dose‐dependently by verapamil (5.1 and 51.0 × 10−7 m).

Adenosine‐induced vascular relaxations were greatly increased in the presence of papaverine (6.1 × 10−7 m) but significantly reduced in the presence of IBMX (4.4 × 10−5 m) or verapamil (5.1 and 51.0 × 10−7 m).

The vasodilatation produced by isoprenaline was increased in the presence of IBMX (4.4 × 10−5 m) or papaverine (6.1 × 10−7 m), but inhibited by verapamil (5.1 and 51.0 × 10−7 m).

The vascular relaxant effects of nitroglycerine and papaverine were inhibited in the presence of IBMX (4.4 × −5 m) or verapamil (5.1 and 51.0 × 10−7 m). Papaverine (6.1 × 10−7 m) also antagonized nitroglycerine‐induced vascular relaxation.

The vasodilator effect of IBMX was greatly reduced in the presence of papaverine (6.1 × 10−7 m) or verapamil (5.1 and 51.0 × 10−7 m).

The vascular relaxant effect of verapamil was reduced proportionally by raising the extracellular Ca2+ concentration from 1.25 to 5.0 mm while those elicited by histamine, adenosine, isoprenaline, nitroglycerine, papaverine and IBMX were not modified by this procedure.

These results were taken as an indication that several vasodilators (e.g. histamine, adenosine, isoprenaline, nitroglycerine, papaverine and IBMX), but not a Ca2+ antagonist such as verapamil, produce a fraction of their vasodilator effects by promoting Ca2+ extrusion from and/or Ca2+ sequestration into the vascular smooth muscle cells, via a cyclic adenosine 3′,5′‐monophosphate‐dependent mechanism.
CENTRAL RESPIRATORY AND CIRCULATORY EFFECTS OF Gymnodinium breve TOXIN IN ANAESTHETIZED CATS
Authors: BORISON HERBERT L. , ELLIS SYDNEY , McCARTHY LAWRENCE E.
Published: July 2012

In cats anaesthetized with pentobarbitone, observations were made on respiration, spontaneous and evoked diaphragmatic electromyograms, blood pressure, heart rate, indirectly‐induced contractions of the anterior tibialis muscle and nictitating membrane, and electrical excitability of the inspiratory centre in the medulla oblongata.

Gymnodinium breve toxin (GBTX) was administered intravenously, intra‐arterially to the brain, and intracerebroventricularly. Physiological effects were recorded while alveolar Pco2 was controlled at a constant level except when changes in gas tension were made in order to measure C02‐ventilatory responsiveness.

Adequate doses of GBTX given intravenously by bolus injection elicited a non‐tachyphylactic reflex response triad of apnoea, hypotension and bradycardia mediated by the vagus nerves independently of arterial baroreceptor and chemoreceptor innervation.

After vagotomy, additional amounts of GBTX (i.v.) resulted in apneustic breathing, hypertension and tachycardia. The cardiovascular effects were abolished by ganglionic blockade with hexamethonium.

Smaller doses of GBTX were required intra‐arterially and intracerebroventricularly than by the intravenous route of injection to produce respiratory irregularity and cardiovascular hyperactivity.

Evoked motor responses, electrical excitability of the medulla oblongata and CO2‐ventilatory responsiveness were largely spared even though GBTX caused marked disturbances in respiratory rhythmicity and cardiovascular functions.

It is concluded that GBTX acts reflexly on vagally innervated receptors to evoke a Bezold‐Jarisch effect but that the toxin further acts centrally to cause irregular breathholding and hypertension with tachycardia, leading ultimately to respiratory and circulatory failure.
EFFECTS OF KETAMINE ON VASCULAR SMOOTH MUSCLE FUNCTION
Authors: ALTURA B.M. , ALTURA B.T. , CARELLA ANTHONY
Published: July 2012

In vitro studies were undertaken on rat aortic strips and portal vein segments to determine whether or not the amine‐type anaesthetic, ketamine, can exert direct actions on vascular smooth muscle.

Ketamine was found to inhibit development of spontaneous mechanical activity and lower basal tension. This action took place with ketamine concentrations found in anaesthetic plasma concentrations, i.e., 1 × 10−5 to 2 × 10−4 m.

Ketamine (10−5 to 10−3 m) dose‐dependently attenuated contractions induced by adrenaline, noradrenaline, angiotensin II, vasopressin and KCl. These inhibitory actions were Observed with ketamine added either before or after the induced contractions.

Ca2+‐induced contractions of K+‐depolarized aortae and portal veins were also attenuated, dose‐dependently, by ketamine.

In contrast to the above inhibitory actions, ketamine (2 × 10−6 to 1 × 10−4 m) was found to potentiate specifically 5‐hydroxytryptamine(5‐HT)‐induced contractions of both aortic and venous smooth muscle. However, this was only observed if ketamine was added after 5‐HT had initiated a contractile response.

All of the inhibitory, as well as 5‐HT‐potentiating, effects were completely, and almost immediately, reversed upon washing out the anaesthetic from the organ baths.

A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects induced by ketamine.

These data suggest that rat plasma concentrations of ketamine commonly associated with induction of surgical anaesthesia can induce, directly, relaxation and contractile potentiation of vascular muscle.

These diverse findings may aid in explaining the well‐known biphasic pressor actions of ketamine.