bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHARMACOLOGICAL ANALYSIS OF HISTAMINE RECEPTORS IN MUSCULATURE AND VASCULATURE OF THE DOG TRACHEA in situ
Authors: HIMORI N. , TAIRA N. 
Published: July 2012

The rôle of histamine Hr and H2‐receptors in the musculature and vasculature of the dog trachea was investigated in the blood‐perfused trachea in situ.
Histamine and acetylcholine caused increases in blood flow (tracheal vasodilatation) and in intraluminal pressure (tracheal constriction) in a dose‐dependent manner. Histamine was almost equi‐potent to acetylcholine in causing tracheal vasodilatation but was about 30 times less potent in causing tracheal constriction.
The histamine H2‐receptor agonist, dimaprit, caused a dose‐dependent increase in tracheal blood flow but failed to cause tracheal constriction.
The tracheal constriction produced by histamine was inhibited strongly by diphenhydramine but not modified by metiamide. The tracheal vasodilatation produced by histamine was antagonized by both diphenhydramine and metiamide; diphenhydramine was more effective than metiamide.
It is concluded that in the tracheal musculature, histamine receptors are exclusively of the Hj‐type and mediate constriction, whereas in the tracheal vasculature, both histamine Hr and H2‐receptors mediate vasodilatation but histamine Hrreceptors are predominant.
RESPONSES OF THE SIMULTANEOUSLY‐PERFUSED HEPATIC ARTERIAL AND PORTAL VENOUS VASCULAR BEDS OF THE DOG TO HISTAMINE AND 5‐HYDROXYTRYPTAMINE
Authors: RICHARDSON P.D.I. , WITHRINGTON P.G. 
Published: July 2012

The sympathetically‐innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously in situ.
Histamine and 5‐hydroxytryptamine (5‐HT) were injected intra‐arterially and intraportally in graded, increasing doses.
Intra‐arterial histamine evoked decreases in hepatic arterial vascular resistance (HAVR) and increases in hepatic portal vascular resistance (HPVR).
Intraportal injections of histamine caused increases in HPVR and decreases in HAVR.
The time courses of the arterial responses to intraportal histamine and of the portal responses to intra‐arterial histamine, compared with any systemic effects, showed that these effects on the liver vasculature could not be the result of recirculation of histamine.
Intra‐arterial 5‐HT evoked biphasic changes in HAVR and small falls in HPVR. Intraportal 5‐HT caused falls in HPVR at low doses and rises at high doses, together, typically, with biphasic effects on HAVR.
It is unlikely that the arterial effects of intraportal 5‐HT and the portal effects of intra‐arterial 5‐HT were due to recirculation of the vasoactive material.
Pathophysiologically, both histamine and 5‐HT are released from the gastrointestinal tract into the portal vein. These experiments show that such release may affect the hepatic arterial vascular resistance (and therefore blood flow) even though vasoactive levels of the autacoids are not attained in the systemic circulation.
THE EFFECTS OF DORSAL BUNDLE INJECTIONS OF 6‐HYDROXYDOPAMINE ON AVOIDANCE RESPONDING IN RATS
Authors: FIBIGER HANS C. , MASON STEPHEN T. 
Published: July 2012

The effects of injection of 6‐hydroxydopamine (6‐OHDA) into the fibres of the dorsal noradrenergic bundle on acquisition, retention and extinction of active avoidance in rats were examined.
6‐OHDA injections severely depleted noradrenaline in all forebrain areas assayed, with the interesting exception of the septum. No significant effect on dopamine concentrations in various forebrain regions was found.
Acquisition and retention of active avoidance was not altered by the lesion. Marked resistance to extinction was seen when the unconditioned stimulus (shock) was removed.
A comparison with work by other authors in which both forebrain noradrenaline and dopamine were depleted suggest that the alteration in extinction seen in both studies is a noradrenergic effect, whereas the deficits in acquisition and retention found previously are dopaminergic in origin.
EVIDENCE FOR TWO DISTINCT TYPES OF POSTSYNAPTIC α‐ADRENOCEPTOR IN VASCULAR SMOOTH MUSCLE in vivo
Authors: DREW G.M. , WHITING SUSAN B. 
Published: July 2012

The effects of the highly selective α1‐adrenoceptor antagonist, prazosin, and the relatively selective α2‐adrenoceptor antagonist, yohimbine, on the pressor responses to intravenous injections of phenylephrine and noradrenaline have been examined in anaesthetized cats and pithed rats in an attempt to determine whether α1‐ and α2‐adrenoceptors are located postsynaptically on vascular smooth muscle.
In anaesthetized cats prazosin caused a much greater reduction in the pressor responses to phenylephrine than to noradrenaline or splanchnic nerve stimulation (after adrenalectomy). Yohimbine was of similar potency in reducing the pressor responses to each stimulus.
A differential blocking activity of prazosin against intra‐arterial injections of phenylephrine and noradrenaline was also demonstrated in the blood‐perfused cat hind limb. As in the whole animal, prazosin was more potent against phenylephrine than noradrenaline. A similar, though less marked, effect was seen in the mesenteric circulation, but not in the renal circulation, where prazosin was almost equipotent in reducing responses to phenylephrine and noradrenaline.
In pithed rats prazosin was a potent, competitive antagonist of phenylephrine, but had little effect against noradrenaline; only the responses to high doses of noradrenaline were reduced by prazosin. Yohimbine was approximately equipotent as an antagonist of phenylephrine and noradrenaline. In the anococcygeus muscle, prazosin was as potent an antagonist of noradrenaline as it was of phenylephrine on vascular smooth muscle.
The results suggest that there are two types of α‐adrenoceptor in the vasculature of cats and rats. Phenylephrine produces pressor responses by stimulating one type of postsynaptic α‐adrenoceptor that is blocked by prazosin and yohimbine; these are α1‐adrenoceptors. Noradrenaline exerts some of its effect via these receptors but most of its effect appears to be exerted through prazosin‐insensitive receptors. The latter receptors appear to differ from α2‐adrenoceptors.
THE CARDIOVASCULAR PHARMACOLOGY OF 7‐PROPYL‐THEOPHYLLINE‐DOPAMINE (D4975); COMPARISON WITH DOPAMINE AND DOBUTAMINE
Authors: McCAIG DOROTHY , PARRATT J.R. 
Published: July 2012

The effects of a newly developed dopamine‐xanthine derivative, 7‐propyl‐theophylline‐dopamine (D4975), have been examined in cats anaesthetized with sodium pentobarbitone. When administered intravenously (in doses as low as 0.5 to 1.0 μg/kg) it increased systemic arterial pressure, left ventricular (LV) dP/dtmax, dP/dt at fixed ventricular isovolumic pressures and cardiac output. Heart rate effects were minimal.
D4975 was about 5 times more active than dopamine or dobutamine in elevating LV dP/dtmax or dP/dt at common peak isovolumic pressures (CPIP) and about 10 times more active than dopamine at increasing systemic arterial blood pressure. The effects of D4975 were also more prolonged than those of the other two agents.
The effects of D4975 on LV dP/dtmax were greatly reduced by the prior administration of propranolol. D4975 has no effect on peripheral β2‐adrenoceptors.
It is suggested that the effects of D4975 on the myocardium involve both β1‐adrenoceptor stimulation and inhibition of phosphodiesterase and that the marked and prolonged pressor response is due to resistance to enzymatic breakdown by monoamine oxidase.
The results suggest that D4975 might prove valuable in the treatment of the hypotension and reduced myocardial contractility of shock, especially as it is possible to select a dose that increases LV dP/dtmax without increasing either heart rate or systemic arterial pressure.
INHIBITION OF INSULIN SECRETION FROM THE PERFUSED PANCREAS OF THE RAT BY PIZOTIFEN
Authors: JOOST H.G. 
Published: July 2012

In the perfused rat pancreas the effects of pizotifen on insulin release induced by 20 mm glucose were studied.
Pizotifen (10 and 100 μm) significantly reduced the insulin release during a 25 min perfusion period to 49% and 7% of the controls.
The same concentrations of the structurally related agents cyproheptadine, doxepin, and chlorpromazine produced a comparable inhibition.
AMINO ACIDS AS NEUROTRANSMITTERS OF CORTICOFUGAL NEURONES IN THE RAT: A COMPARISON OF GLUTAMATE AND ASPARTATE
Authors: STONE TREVOR W. 
Published: July 2012

The relative sensitivities to aspartate and glutamate of neurones receiving a corticofugal innervation were examined by microiontophoresis, and compared with the relative sensitivities of neurones not appearing to receive such an input.
On all the cells tested, glutamate appeared to be a more potent excitant than aspartate in terms of neuronal response size or effective dose.
dl‐α‐Aminoadipate (αAA) reduced the excitatory amino acid responses on all the neurones tested. On many of these cells a control excitation could be produced, by acetylcholine or hydrogen ions, which was in most cases unaffected by doses of αAA producing antagonism of amino acid excitation.
On 70% of the cells, aminoadipate showed no selectivity for aspartate compared with glutamate but a differential action, involving blockade of aspartate but not glutamate, was apparent on the other 30%.
Doses of αAA which selectively reduced responses to aspartate had no effect on short latency evoked spikes, but doses which also reduced responses to glutamate reduced the short‐latency synaptic excitation induced by electrical stimulation of either the surface of the cerebral cortex, or of the pyramidal tracts in the medulla.
These findings suggest that corticofugal neurones having an excitatory action on cells in various parts of the brain may use an amino acid, probably glutamate, as a common neurotransmitter.
As no significant difference could be demonstrated in the potency ratios of glutamate aspartate on monosynaptically activated cells compared with other cells, doubt is cast on the validity of drawing conclusions about transmitter identity from potency ratios alone, without the support of antagonist studies.
EFFECTS OF UPTAKE INHIBITORS ON RESPONSES OF SHEEP CORONARY ARTERIES TO CATECHOLAMINES AND SYMPATHETIC NERVE STIMULATION
Authors: BRINE F. , CORNISH E.J. , MILLER R.C. 
Published: July 2012

Transmural stimulation of intrinsic sympathetic nerves and exogenous catecholamines produce β1‐adrenoceptor mediated relaxant responses in strips of contracted sheep coronary artery.
The neuronal uptake inhibitors, metaraminol, cocaine and desipramine and the extraneuronal uptake inhibitor, cortisol, failed to potentiate responses to noradrenaline or sympathetic stimulation; responses to isoprenaline were enhanced by cortisol.
Oxytetracycline, which inhibits binding to connective tissue fibres, did not affect responses to noradrenaline or nerve stimulation.
17β‐Oestradiol, caffeine and U0521 proved to be unsuitable compounds for studying catecholamine inactivation since they non‐selectively potentiated responses to noradrenaline and isoprenaline.
It is concluded that catecholamine inactivation processes do not modify transmitter function in sheep coronary arteries.
ANTAGONISM OF EXCITATORY AMINO ACID‐INDUCED RESPONSES AND OF SYNAPTIC EXCITATION IN THE ISOLATED SPINAL CORD OF THE FROG
Authors: EVANS R.H. , FRANCIS A.A. , HUNT K. , OAKES D.J. , WATKINS J.C. 
Published: July 2012

A range of compounds has been tested for excitatory amino acid agonist or antagonist activity and for effects on synaptic activity on isolated hemisected spinal cords of frogs.
l‐Monoamino dicarboxylic acids of chain length up to 8 carbon atoms (l‐α‐aminosuberate) were all agonists.
Within a series of d‐monoamino dicarboxylic acids, and with diamino dicarboxylic acids (mainly unresolved mixtures of diasteroisomers), there was a progression from agonist activity, for compounds of chain length equal to or shorter than glutamate, to antagonist activity, for compounds of longer chain length. d‐α‐Aminosuberate (DαAS) was the most potent antagonist.
The antagonist actions of these substances showed a Mg2+ ‐like selectivity with respect to depolarizations produced by different excitants. N‐methyl‐d‐aspartate (NMDA) was the most susceptible agonist and quisqualate and kainate the least susceptible. Responses to other excitatory amino acids, including l‐glutamate and l‐aspartate, showed intermediate sensitivity to the antagonists.
A parallelism was observed between the relative potencies of mono‐ and diamino dicarboxylic acids as NMDA antagonists and their relative potencies as depressants of synaptic responses.
The results support the concept of different types of excitatory amino acid receptors, with NMDA and its antagonists acting predominantly on one type. These NMDA receptors are probably transmitter receptors activated by an excitatory amino acid transmitter.
PHARMACOLOGICAL PROPERTIES OF KRYPTOPYRROLE AND ITS OXIDATION PRODUCTS ON ISOLATED SCIATIC NERVE OF RAT AND ON GUINEA‐PIG ILEUM
Authors: GORCHEIN A. , MITCHELL L.D. , ROGERS A.T. 
Published: July 2012

Kryptopyrrôle (2, 4‐dimethyl, 3‐ethylpyrrôle) inhibited conduction in rat sciatic nerve by a local anaesthetic action.
Tone and both spontaneous and electrically‐induced contractions of guinea‐pig ileum were also inhibited by kryptopyrrôle. The concentration of kryptopyrrôle required for 50% inhibition of a maximum twitch tension (ID50) was 0.085 him.
Oxidation products of kryptopyrrôle with chromatographic properties similar to those of urinary constituents reported in schizophrenia and hepatic porphyrias had little or no effect at similar concentrations.
Dose‐response curves to exogenous acetylcholine in guinea‐pig ileum were shifted to the right by kryptopyrrôle, with loss of parallelism and reduction in the maximum contraction.
Acetylcholine overflow from ileal segments at rest and during electrical stimulation was reduced by kryptopyrrôle.
These results on ileal segments are consistent with kryptopyrrôle having both a post‐junctional site of action, presumably directly on the muscle, and a pre‐junctional site reducing the output of acetylcholine from the myenteric plexus.
The significance of these findings is discussed in relation to a possible clinical pathological rôle for these compounds.
MYOCARDIAL SYNTHESIS OF PROSTAGLANDIN‐LIKE SUBSTANCES AND CORONARY REACTIONS TO CARDIOSTIMULATION AND TO HYPOXIA
Authors: SUNAHARA F.A. , TALESNIK J. 
Published: July 2012

Continuous recording of cardiac contractions and coronary flow from isolated perfused hearts of rats permitted the study of coronary reactions to: (a) cardiostimulation induced by single doses or slow infusions of noradrenaline, CaCl2, glucagon or electrically induced tachycardia; (b) short interruptions of coronary inflow (hypoxia).
Except during tachycardia the heart rate was kept constant at 210 beats/min by electrical pacing.
Metabolic coronary vasodilatation (MCD) resulting from cardiac hyperactivity induced by noradrenaline, Ca2+, tachycardia or glucagon was inhibited by administration of prostaglandin E2. Reactive hyperaemia response to hypoxia was unaffected by prostaglandin administration.
Inhibition of MCD could also be obtained by prolonged infusion with arachidonic acid (1.6 × 10−7m), presumably by its conversion into prostaglandin‐like substance since arachidonic acid failed to block MCD in hearts from rats pretreated with non‐steroidal anti‐inflammatory drugs (indomethacin, naproxen, phenylbutazone).
Reactive hyperaemia was unaffected either by arachidonic acid or by blockade of the synthesis of prostaglandin‐like substances by anti‐inflammatory drugs.
Since prostaglandin synthetase inhibition does not prevent but may enhance MCD, we do not advocate prostaglandin‐like substances as agents directly responsible for the coronary vasodilatation that follows cardiac hyperactivity.
We postulate that cardiac overproduction of prostaglandins may lead to a failure in the adaptive coronary flow response to cardiac hyperactivity (coronary insufficiency?).
EFFECTS OF ADENOSINE 5′‐TRIPHOSPHATE (ATP) AND β‐γ‐METHYLENE ATP ON THE RAT URINARY BLADDER
Authors: BROWN C. , BURNSTOCK G. , COCKS T. 
Published: July 2012

High concentrations of adenosine 5′‐triphosphate (ATP, 100 to 1000 μm) were required to cause contraction of the rat urinary bladder, while adenosine and adenosine 5′‐monophosphate (AMP, 1 to 50/im) produced relaxation.
One hundred fold lower concentrations of β‐γ‐methylene ATP, which is resistant to degradation to AMP and adenosine, caused dose‐dependent, phasic contractions which mimicked atropine‐resistant responses to nerve stimulation.
Adenosine and AMP caused dose‐dependent inhibition of carbachol‐induced contractions; theophylline competitively antagonized this inhibition but not the contractile responses to β‐γ‐methylene ATP, ATP or atropine‐resistant nerve stimulation.
These results suggest that the insensitivity of the rat bladder to ATP is due to its rapid degradation to AMP and adenosine and support the hypothesis that the bladder receives a purinergic excitatory innervation.
DEPRESSION OF DRUG METABOLISM IN THE MOUSE BY A COMBINATION OF Mycobacterium butyricum AND ANAESTHETICS
Authors: BARBIERI EDWARD J. , CIACCIO EDWARD I. 
Published: July 2012

Subcutaneous injection of Mycobacterium butyricum suspended in mineral oil into the mouse hind paw caused an oedematous local inflammation. Hind paw swelling was maximum 5 days after injection and was still apparent at day 30.
Drug metabolism in vivo (as monitored by ketamine‐ or pentobarbitone‐induced sleeping times) was not affected by the inflammatory disease. However, administration of ketamine or pentobarbitone at day 1 led to significantly elevated sleeping times when the mice showing local inflammation were retested at day 5 with the anaesthetics.
Indomethacin inhibited hind paw oedema in the mouse but did not affect ketzmine‐Mycobacter‐ium butyricum‐induced depression of drug metabolism.
Prolongation of ketamine‐induced anaesthesia by combination with Mycobacterium butyricum at day 5 correlated with the degree of hind paw inflammation at this time.
The data suggest that anaesthetics (i.e., ketamine and pentobarbitone) may sensitize hepatic membranes to the effect of Mycobacterium butyricum or some toxic compound elaborated during the active phase of inflammation.
DIFFERENTIATION OF THE ROLES OF HISTAMINE Hr AND H2‐RECEPTORS IN THE MEDIATION OF THE EFFECTS OF HISTAMINE IN THE ISOLATED WORKING HEART OF THE GUINEA‐PIG
Authors: FLYNN SHEILA B. , GRISTWOOD R.W. , OWEN D.A.A. 
Published: July 2012

Differentiation of the rôles of histamine Hr and H2‐receptors in the mediation of the effects of histamine on the isolated working heart of the guinea‐pig was achieved through the use of histamine and selective histamine receptor agonists and antagonists.
Histamine over the dose range 10−9mol to 10−6mol produced dose‐related increases in sinus rate, left intraventricular pressure (LVP)max, LVdP/dtmax, coronary flow, aortic flow, total cardiac output and external pressure‐volume work.
Dimaprit, a selective histamine H2‐receptor agonist, produced very similar responses to histamine.
2‐Pyridylethylamine, a selective histamine Hj‐receptor agonist, had little effect on cardiac function unless large doses were administered. Such doses produced increases in all measured parameters.
Cimetidine, a selective histamine H2‐receptor antagonist, antagonized the effects of histamine and dimaprit and some but not all effects of 2‐pyridylethylamine. In the presence of cimetidine a decrease in all parameters with the exception of sinus rate was observed with both histamine and 2‐pyridylethylamine.
The selective histamine Hi‐receptor antagonist, mepyramine, had little effect on responses to all three agonists. However, the depressant effects observed with histamine and 2‐pyridylethylamine in the presence of cimetidine were antagonized by mepyramine.
The results indicate the important rôle of the histamine H2‐receptor in the mediation of the gross cardiac effects of histamine and also indicate that histamine Hx‐receptors can mediate cardiac depression.
EFFECT OF Gymnodinium breve TOXIN IN THE RAT PHRENIC NERVE DIAPHRAGM PREPARATION
Authors: GALLAGHER JOEL P. , SHINNICK‐GALLAGHER PATRICIA 
Published: July 2012

The effects of a crude fraction of Gymnodinium breve toxin (GBTX) were studied on the rat phrenic nerve diaphragm preparation.
Indirectly stimulated muscle contractions were more sensitive to blockade by increasing concentrations of GBTX (0.25 μg/ml to 10 μg/ml) than direct muscle contractions.
GBTX increased miniature endplate potential (m.e.p.p.) frequency and depolarized the resting membrane potential of the muscle fibres at the endplate and in non‐synaptic regions of muscle fibre.
A concentration‐dependent biphasic effect on m.e.p.p. amplitude was evident. At lower concentrations m.e.p.p. amplitudes were depressed whereas at high concentrations they were increased.
GBTX blocked endplate potentials (e.p.ps) in concentrations (0.5 μg/ml to 2 μg/ml) that did not block m.e.p.ps.
Muscle fibre action potentials recorded from cells held at control membrane potential by hyperpolarizing current were not altered by toxin treatment. No repetitive e.p.ps, or muscle action potentials were observed.
These data suggest that GBTX may block indirectly stimulated muscle contractions and e.p.ps by depolarizing the nerve terminal in a manner similar to the observed depolarization of the muscle fibre. The depolarization of the nerve terminal may be sufficient to inhibit transmitter release.
EFFECTS OF OXYTOCIN ON THE ISOLATED VAS DEFERENS OF THE RAT
Authors: BENEIT JUAN V. , HIDALGO AGUSTIN , TAMARGO JUAN L. 
Published: July 2012

The effect of oxytocin was studied on the isolated vas deferens of the rat.
Oxytocin (25 to 200 mu/ml) reversibly reduced the contractile response induced by noradrenaline, dopamine and acetylcholine.
Oxytocin (400 mu/ml) abolished the response to potassium.
The contractions evoked in the vas deferens by field stimulation were also reduced by oxytocin (50 to 200 mu/ml). The inhibitory effect of the drug was related to the external calcium concentration.
It is suggested that oxytocin depresses the contractile responses in the vas deferens at least partly by reducing the availability of calcium from an extracellular source.