bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE NEURONAL ORIGIN OF PROSTAGLANDIN RELEASED FROM THE RABBIT PORTAL VEIN IN RESPONSE TO ELECTRICAL STIMULATION
Authors: GREENBERG R. 
Published: July 2012

Transmural electrical stimulation of the isolated portal vein of the rabbit was accompanied by the release of a prostaglandin‐like substance (PLS). Thin layer chromatography coupled with bioassay indicated that this substance was probably prostaglandin E2 (PGE2).
Indomethacin potentiated the response of the portal vein to electrical stimulation at 2 Hz and abolished the release of the PLS.
There was no significant change in the amount of PLS released from the portal vein in response to electrical stimulation at 2 Hz when the contractile response of the portal vein was prevented by pretreatment with phentolamine or guanethidine.
In vitro denervation of the portal vein with 6‐hydroxydopamine or the omission of Ca2+ from the bathing solution caused a significant reduction in the amount of PLS released from the portal vein in response to electrical stimulation at 2 hertz.
It is concluded that electrical stimulation of the isolated portal vein of the rabbit is accompanied by the release of a PLS, probably PGE2, from a neuronal source. The synthesis and release of the PLS is Ca2+‐dependent.
PURINERGIC INNERVATION OF THE GUINEA‐PIG URINARY BLADDER
Authors: BURNSTOCK G. , COCKS T. , CROWE R. , KASAKOV L. 
Published: July 2012

A number of criteria for considering adenosine 5′‐triphosphate (ATP) as a neurotransmitter in the guinea‐pig urinary bladder have been examined. In addition, the effect of tachyphylaxis to ATP on the response to non‐adrenergic, non‐cholinergic nerve stimulation has been re‐examined.
Quinacrine fluorescence histochemistry revealed a population of nerve fibres, ganglion cells, and nerve bundles in the bladder which were not seen in either the iris or vas deferens, where adrenergic and cholinergic nerves predominate. The distribution and morphology of the quinacrine‐positive nerves in the bladder were different from those observed with catecholamine fluorescence and cholinesterase histochemistry, and were unaffected by chemical sympathectomy.
Release of ATP from the bladder during stimulation of intramural excitatory nerves, in the presence of atropine and guanethidine increased to 3–12 times prestimulation levels. Tetrodotoxin abolished both the contractile response and the increase in ATP release resulting from intramural nerve stimulation. There was no increase in ATP release during contraction resulting from direct muscle stimulation following nerve paralysis with tetrodotoxin.
Sympathectomy with 6‐hydroxydopamine did not affect release of ATP in response to intramural nerve stimulation.
Release of ATP was dependent on the concentration of calcium ion in the medium.
Contractions in response to non‐adrenergic, non‐cholinergic intramural nerve stimulation were closely mimicked by ATP, but not by acetylcholine or histamine.
Adenosine and dipyridamole reduced the contractions to both ATP and non‐cholinergic nerve stimulation.
2–2′‐Pyridylisatogen was not a specific blocker of either ATP or intramural nerve stimulation in the guinea‐pig bladder. 2‐Substituted imidazolines initiated spontaneous activity making it impossible to assess any blocking action that they may have had.
Prostaglandins (E1 E2 and F2a) gave weak, slow contractions and an increase in spontaneous activity. Both the response to ATP and non‐adrenergic, non‐cholinergic nerve stimulation were greatly potentiated in the presence of prostaglandins.
In the presence of indomethacin the response to non‐adrenergic, non‐cholinergic nerve stimulation was virtually abolished following desensitization to ATP.
EFFECT OF MECAMYLAMINE ON THE FATE OF DOPAMINE IN STRIATAL AND MESOLIMBIC AREAS OF RAT BRAIN; INTERACTION WITH MORPHINE AND HALOPERIDOL
Authors: AHTEE LIISA , KAAKKOLA SEPPO 
Published: July 2012

The effects of the nicotinic cholinoceptor blocking drug, mecamylamine (alone or in combination with morphine or haloperidol) were investigated on the striatal homovanillic acid (HVA) concentration and on the α‐methyl‐p‐tyrosine (AMPT)‐induced depletion of striatal or mesolimbic dopamine content in the brain of rats.
Mecamylamine (2 mg/kg) alone did not alter the striatal HVA concentration, but it reduced the probenecid‐induced accumulation of HVA. Mecamylamine pretreatment reduced the morphine‐and haloperidol‐induced elevation of striatal HVA concentration. Hexamethonium did not alter the striatal HVA concentration when given alone or in probenecid‐ or morphine‐treated rats, whereas pempidine (8 mg/kg) clearly reduced the probenecid‐induced accumulation of HVA in the striatum.
Mecamylamine (2 and 8 mg/kg) slowed the rate of AMPT‐induced depletion of dopamine from the striatum and mesolimbic area both in the brain of control rats and of rats treated with morphine or haloperidol.
Mecamylamine slightly prolonged the cataleptic effect of morphine.
The results indicate that mecamylamine inhibits the release of dopamine both from the striatal and mesolimbic dopaminergic neurones.
THE UPTAKE KINETICS AND METABOLISM OF EXTRANEURONAL NORADRENALINE IN GUINEA‐PIG TRACHEA AS STUDIED WITH QUANTITATIVE FLUORESCENCE MICROPHOTOMETRY
Authors: O'DONNELL STELLA R. , SAAR NILI 
Published: July 2012

Extraneuronal uptake of noradrenaline and α‐methylnoradrenaline into single cells of guinea‐pig tracheal smooth muscle have been studied by means of quantitative fluorescence microphotometry.
Fluorescence brightness due to accumulation of α‐methylnoradrenaline was dose‐dependent and was increased by the catechol‐O‐methyltransferase inhibitor drugs, tropolone or β‐thujaplicin (200 μM) but not by 3,4‐dimethoxy‐5‐hydroxybenzoic acid (200 μM).
Fluorescence brightness due to accumulation of noradrenaline was increased if animals were pretreated with the monoamine oxidase inhibitor drug, nialamide.
The study suggests that metabolism of amines by catechol‐O‐methyltransferase and monoamine oxidase can occur subsequent to extraneuronal uptake in guinea‐pig tracheal smooth muscle.
The uptake of noradrenaline into tracheal smooth muscle was concentration‐dependent, saturable, and had a Km of 156 μM.
THE ACTIONS OF SOME VASOACTIVE POLYPEPTIDES AND THEIR ANTAGONISTS ON THE ANOCOCCYGEUS MUSCLE
Authors: GILLESPIE J.S. , McKNIGHT A.T. 
Published: July 2012

The action of three polypeptides, bradykinin, substance P and eledoisin known to inhibit vascular smooth muscle has been examined on the anococcygeus muscle of the rat, cat and rabbit.
In the atonic rat muscle, bradykinin and substance P had little or no effect on tone but eledoisin produced a sustained dose‐related contraction which could be abolished by phentolamine (1 μM) and is, therefore, probably an indirect sympathomimetic effect. On the motor response to field stimulation of adrenergic nerves, bradykinin had no effect whereas both substance P and eledoisin reduced this response. The mechanism of action was further analysed with eledoisin by examining its effect on the response to noradrenaline. Eledoisin did not alter the dose‐response curve to noradrenaline and its inhibitory action is likely, therefore, to be presynaptic.
In the rat anococcygeus muscle in which the tone was raised by guanethidine or carbachol, bradykinin and substance P reduced this tone whereas eledoisin continued to exert a motor action. Compared with substance P the inhibitory effect of bradykinin appeared at lower concentrations (threshold 0.01 μg/ml), developed more rapidly and the size of the response was greater.
The effect of bradykinin on the tonically contracted cat and rabbit anococcygeus muscles was examined in addition to that of the rat. In all three species bradykinin caused inhibition and the magnitude of the response was equal to the maximum effect of inhibitory nerve stimulation. None of the peptides affected the inhibitory response to nerve stimulation itself.
The effects of three substances, hesperitin, khellin and apiin, reported in other tissues to antagonize the action of bradykinin were examined both on the inhibitory response to bradykinin and to field stimulation. None of them was able to inhibit either response, although they reduced tone when given by themselves. During these experiments it was found that ethanol antagonized the inhibitory response to field stimulation.
The possibility that bradykinin or some related peptide might play a part in the inhibitory response to nerve stimulation in the anococcygeus is discussed.
β‐ADRENOCEPTOR MEDIATED INHIBITION BY TERBUTALINE OF HISTAMINE EFFECTS ON VASCULAR PERMEABILITY
Authors: O'DONNELL STELLA R. , PERSSON C.G.A. 
Published: July 2012

In guinea‐pigs, previously given Evans blue dye intravenously, 13 to 18 intradermal injections of histamine, with or without other drugs, were made into the depilated trunk skin. Dye was then quantitatively extracted from each skin area and the measured absorbance values were used as a measure of vascular leakage of macromolecules.
Histamine (0.5 to 12 nmol) produced dose‐related increases in vascular leakage. These were reduced by terbutaline (1 and 10 nmol) which produced a significant shift in the histamine dose‐response lines to lower absorbance values. The effect of 0.1 nmol of terbutaline was significant only against doses of histamine of less than 2 nmol.
Propranolol (1 nmol and 10 nmol) antagonized the effects of terbutaline. Propranolol, at a dose of 10 nmol but not 1 nmol, itself reduced the responses to 1.5 nmol histamine.
We conclude that the inhibition by terbutaline of histamine‐induced dye leakage in guinea‐pig skin is mediated by stimulation of β‐adrenoceptors and it is suggested that this effect of terbutaline occurs directly on β‐receptors at the vascular leakage site.
PREVENTION BY GUANETHIDINE ANALOGUES OF OUTPUT OF NORADRENALINE INDUCED BY SODIUM REDUCTION IN RABBIT VENTRICULAR SLICES
Authors: HOSOTANI T. , MISU Y. 
Published: July 2012

The prevention by guanethidine and related agents of the output of noradrenaline induced by low sodium was investigated in rabbit ventricular slices. When external NaCl was reduced, the output of noradrenaline into the medium collected at 30 min intervals, increased and the endogenous levels decreased. These changes induced by replacing sodium with sucrose or choline were not affected either by the omission of calcium and addition of 0.5 mm ethylene glycol‐bis(aminoethyl‐ether)N,N,N′,N′ tetra‐acetic acid (EGTA) or by an increase in the calcium concentration to 10 mm 30 min before sodium deprivation.
Guanethidine 4 × 10−6 and 4 × 10−5m and 4–7‐exo‐methylene‐hexahydroisoindoline‐ethyl guanidine (No. 865‐123) 4 × 10−5 to 8 × 10−4m inhibited, in a dose‐dependent manner, increases in output of noradrenaline induced by reduction of sodium to 18 mm, while guanethidine 8 × 10−5m and high doses of bretylium produced no inhibition: the latter two released noradrenaline.
The inhibitory actions of guanethidine 4 × 10−5m and No. 865‐123 4 × 10−4m were prevented by tetracaine 3.3 × 10−4m, which per se did not modify the output of noradrenaline induced by 18 mm sodium.
Accumulation of guanethidine and No. 865‐123 in ventricular slices was greater than that noted in striated muscle slices and was dose‐, time‐ and temperature‐dependent. Tetracaine 3.3 × 10−4m did not prevent the accumulation of guanethidine 4 × 10−5m and No. 865‐123 1.1 × 10−6 to 4 × 10−4m.
The guanidine derivatives appear to increase the permeability of adrenergic nerve endings to sodium ions.
THE POSTNATAL DEVELOPMENT OF ADRENOCEPTOR RESPONSES TO AGONISTS AND ELECTRICAL STIMULATION IN RAT ISOLATED ATRIA
Authors: STANDEN N.B. 
Published: July 2012

Isolated right and left atria from rats of ages ranging from newborn to adult were used to measure chronotropic and inotropic responses to noradrenaline, isoprenaline, tyramine, and electrical stimulation of intramural nerves.
Right atria from newborn animals showed increases in rate with noradrenaline, isoprenaline, and tyramine which did not differ significantly from those of atria from adults. The ED50 values for the chronotropic actions of noradrenaline and isoprenaline were not significantly different at any age from the values in adult preparations.
Paced left atria from newborn rats showed well developed positive inotropic responses to noradrenaline and isoprenaline. Newborn left atria (and those from 1 and 2 week old animals) were supersensitive to noradrenaline but not to isoprenaline.
Left atria from newborn animals showed very small inotropic responses to both tyramine and field stimulation of intramural nerves. These responses developed progressively with age over the first three weeks of life. The results are discussed with respect to the development of cardiac β‐adrenoceptors and of cardiac sympathetic innervation.
THE INFLUENCE OF L‐TRYPTOPHAN AND MONOAMINE OXIDASE INHIBITORS ON CATECHOLAMINE METABOLISM IN RAT BRAIN
Authors: ECCLESTON D. , NICOLAOU N. 
Published: July 2012

L‐Tryptophan (100 mg/kg) was administered to rats with or without pretreatment with a monoamine oxidase inhibitor and the concentration of 5‐hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3‐methoxy 4‐hydroxyphenyl glycol, normetanephrine, noradrenaline and dopamine measured in whole brain one hour later.
L‐Tryptophan increased the concentration of 5‐hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3‐methoxy 4‐hydroxyphenyl glycol and normetanephrine. The concentration of noradrenaline did not change whilst that of dopamine increased significantly.
In animals pretreated chronically with a monoamine oxidase inhibitor, tryptophan increased the concentration of dihydroxyphenylacetic acid and homovanillic acid compared to monoamine oxidase alone.
The results suggest either a release of dopamine and noradrenaline by 5‐hydroxytryptamine, with a compensatory increase in their synthesis, or an increase in the firing of dopaminergic and noradrenergic neurones after L‐tryptophan.
MODELS FOR INVESTIGATING THE AETIOLOGY OF CEREBRAL ARTERIAL SPASM: COMPARATIVE RESPONSES OF THE HUMAN BASILAR ARTERY WITH RAT COLON, ANOCOCCYGEUS, STOMACH FUNDUS, AND AORTA AND GUINEA‐PIG ILEUM AND COLON
Authors: BOULLIN D.J. , HUNT TERESA M. , ROGERS A.T. 
Published: July 2012

The pharmacological similarity between human basilar artery and a number of isolated tissues (rat colon, anococcygeus, stomach fundus and aorta and guinea‐pig ileum and colon) has been assessed during investigations of the aetiology of cerebral arterial spasm.
The responses of each of the six tissues to human normal and abnormal cerebrospinal fluid (CSF) and to human serum were compared with those of the human isolated basilar artery.
These studies revealed the presence of a vasodilator factor in CSF from subarachnoid haemorrhage patients and several tissues may be of use for further work in identifying the vasoactive substances in CSF.
No tissue displayed exactly the same spectrum of biological reactivity as the human basilar artery. The rat stomach fundus showed the closest similarity and was further studied for similarities in drug‐induced responses.
The rat stomach fundus, like the human basilar artery, was contracted by 5‐hydroxytryptamine, prostaglandin F2a and histamine and relaxed by dopamine. However, noradrenaline relaxed the fundus but contracted the basilar artery.
THE EFFECT OF AMITRIPTYLINE ON PRESYNAPTIC MECHANISMS IN NORADRENERGIC NERVES
Authors: HUGHES I.E. 
Published: July 2012

Electrically evoked and resting overflow of tritium was measured from mouse vas deferens previously incubated with [3H]‐(—)‐noradrenaline.
At low concentrations (1.6 × 10−7 to 4 × 10−6m) amitriptyline increased only the evoked tritium overflow while higher concentrations increased both evoked and resting overflow.
In the presence of atropine (1 × 10−6m) amitriptyline still produced an increase in evoked tritium overflow.
In the presence of a concentration of cocaine (1.1 × 10−5m) which produced a maximal blockade of the uptake of exogenous noradrenaline the application of amitriptyline still produced an increase in evoked tritium overflow.
In the presence of a concentration of phentolamine (1 × 10−5m) that produced complete blockade of the presynaptic α‐adrenoceptors, amitriptyline still produced an increase in evoked tritium overflow.
In the presence of cocaine and phentolamine together the effect of amitriptyline on evoked overflow was abolished.
It is concluded that amitriptyline may raise synaptic levels of noradrenaline by blocking presynaptic α‐adrenoceptors controlling noradrenaline release and by blocking its uptake into sympathetic neurones.
RELATIONSHIP BETWEEN ATRIAL AND VENTRICULAR RATES OF FIBRILLATION AND CARDIAC CONTRACTILE TISSUE EFFECTIVE REFRACTORY PERIODS IN THE DOG
Authors: FARGES J.P. , FAUCON G. , LIEVRE M. , OLLAGNIER M. 
Published: July 2012

During total cardiopulmonary bypass, acetylcholine‐, isoprenaline‐, ouabain‐ and quinidine‐induced variations in the atrial and ventricular rates of fibrillation were studied and compared with the variations in effective refractory periods (ERP) of atrial and ventricular contractile tissue obtained under the same experimental conditions.
Acetylcholine significantly shortened the ERP and accelerated the rate of fibrillation in the atrium but did not provoke any change in ventricular tissue. A parallel decrease in atrial and ventricular ERP and a parallel increase in atrial and ventricular rates of fibrillation were observed with isoprenaline.
Ouabain exerted a biphasic effect on the atrium, with an initial decrease in the ERP and an initial acceleration of the rate of fibrillation. It produced only a slight decrease in the ventricular ERP and no significant variation in the ventricular rate of fibrillation.
Quinidine induced a greater increase in the ERP and a greater slowing of the rate of fibrillation in the atrium than in the ventricle.
The variations in percentage change of refractoriness and rate of fibrillation were strictly correlated: r = 0.89 (P > 0.001); the equation of the regression line was y = −0.86 × −2.98.
PROSTAGLANDIN PRODUCTION BY MACROPHAGES AND THE EFFECT OF ANTI‐INFLAMMATORY DRUGS
Authors: BRAY M.A. , GORDON D. 
Published: July 2012

Macrophages derived from peritoneal cavity inflammatory exudates of guinea‐pigs produced substantial amounts of prostaglandin E2‐like activity during in vitro culture, so providing the basis for an experimental model of prostaglandin production during inflammatory reactions.
Dose‐related inhibition of prostaglandin biosynthesis was demonstrated by 16 acidic non‐steroidal anti‐inflammatory drugs.
Seven anti‐inflammatory glucocorticosteroid preparations inhibited prostaglandin production in a dose‐related manner. The relative potencies of dexamethasone, prednisolone and hydrocortisone were consistent with clinical anti‐inflammatory ranking. Cortisone, however, failed to inhibit macrophage prostaglandin production.
Three other agents used in the treatment of inflammatory joint diseases were examined. Sodium aurothiomalate inhibited prostaglandin production, although higher concentrations were toxic to macrophages. D‐Penicillamine did not affect macrophage prostaglandin production. Colchicine, in contrast, enhanced prostaglandin production at some concentrations.
The probable significance of macrophages as a source of prostaglandins, during inflammatory responses, is discussed.
DIFFERENCES BETWEEN PRESYNAPTIC AND POSTSYNAPTIC α‐ADRENOCEPTORS IN THE ISOLATED NICTITATING MEMBRANE OF THE CAT: EFFECTS OF METANEPHRINE AND TOLAZOLINE
Authors: ARBILLA SONIA , LANGER S.Z. 
Published: July 2012

The α‐adrenoceptor blocking agent, tolazoline, and the O‐methylated metabolite of adrenaline, metanephrine, produced a concentration‐dependent increase of tension in the smooth muscle of the cat isolated nictitating membrane. These effects were considered to be due to the activation of postsynaptic α‐adrenoceptors.
The responses to nerve stimulation of this muscle were neither potentiated nor blocked by tolazoline (0.1 to 10 μm) or metanephrine (1 to 10 μm).
3H‐transmitter overflow evoked by electrical stimulation was not modified by tolazoline or metanephrine in concentrations in which these drugs stimulated the postsynaptic α‐adrenoceptors.
Since tolazoline and metanephrine failed to activate the presynaptic α‐adrenoceptors of the cat nictitating membrane under experimental conditions in which they stimulated the postsynaptic α‐adrenoceptors, these results further support the view that the presynaptic (a2) adrenoceptors differ from the postsynaptic (a1) adrenoceptors.
CARDIOVASCULAR EFFECTS OF ACEBUTOLOL FOLLOWING CORONARY ARTERY OCCLUSION AND REPERFUSION IN ANAESTHETIZED DOG
Authors: CHERNECKI W. , DAS P.K. , DHALLA N.S. , SHARMA G.P. 
Published: July 2012

The effects of 5 mg/kg acebutolol given intravenously were investigated in anaesthetized dogs after (a) ligation of the left anterior descending coronary artery and (b) coronary reperfusion following 60 min of ligation of the left anterior descending coronary artery.
Coronary artery ligation produced, after 4 to 6 h, persistent multiple ventricular ectopic beats and abnormalities of R and T waves and of the S‐T segment. Administration of acebutolol, after the development of persistent ventricular arrhythmias, restored normal sinus rhythm within 5 min of injection. Electrocardiographic abnormalities were also reduced.
Coronary artery reperfusion (following 60 min of ligation) resulted in multiple ventricular ectopic beats, ventricular tachycardia and/or ventricular fibrillation. Pretreatment with acebutolol, 15 min before starting reperfusion, markedly reduced the arrhythmias.
Acebutolol did not affect peak inspiratory airway pressure.
Acebutolol produced significant bradycardia and slight, transient, hypotension. It was without effect on left ventricular systolic pressure, left ventricular end‐diastolic pressure, cardiac output or pulmonary arterial pressure.
These results suggest beneficial effects of acebutolol in myocardial ischaemia and coronary reperfusion, without any significant risk of cardiodepression or bronchospasm.
THE PHARMACOKINETICS OF LITHIUM IN THE BRAIN, CEREBROSPINAL FLUID AND SERUM OF THE RAT
Authors: WRAAE O. 
Published: July 2012

Addition of lithium carbonate (55 mmol/kg dry wt.) to the diet of rats for 4 days resulted in ratios between lithium in the brain and serum and between the cerebrospinal fluid (CSF) and serum of approx. 1 and 0.4, respectively. The relationships between the concentrations were linear.
After single intraperitoneal injections of lithium chloride (5 mmol/kg body wt.) the concentration of lithium in the CSF was greater than that of the brain for 2 h.
Repeated subcutaneous injections of lithium chloride (0.9 mmol/kg body wt.) resulted in steady state ratios corresponding to those observed when lithium was given in the diet. The rate of elimination from the CSF was intermediate between that of the serum and cerebral tissue until a new equilibrium was reached after approx. 24 h. At that time the ratios between lithium in the brain and serum, and in the CSF and serum were increased to approx. 5 and 0.8, respectively.
These results are consistent with passive transfer kinetics of lithium in the CSF and elimination of lithium from the cerebral tissue via the CSF.
The results may explain some of the phenomena observed in patients during intoxication with lithium.
DEMONSTRATION OF 5‐HYDROXYTRYPTAMINE RECEPTORS THROUGH INHIBITION BY METHERGOLINE IN CAT PIAL ARTERIES in vitro
Authors: EDVINSSON L. , HARDEBO J.E. 
Published: July 2012

In an attempt to characterize further the nature of the 5‐hydroxytryptamine (5‐HT)‐induced contraction of intracranial vessels, cat's middle cerebral artery was exposed to this amine and the specific 5‐HT receptor antagonist, methergoline, under standardized conditions in vitro. Methergoline, in increasing concentrations, produced a parallel shift of the log dose‐response curve for 5‐HT.
The Arunlakshana‐Schild plot gave a straight line with a slope of −0.85. The figure corresponding to the pA2 value was 8.80.
The findings offer further support for the assumption that the 5‐HT‐induced intracranial vasoconstriction is mediated by specific 5‐HT receptors.