bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.