bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF MODULATORS OF ARACHIDONIC ACID METABOLISM ON THE SYNTHESIS AND RELEASE OF SLOW‐REACTING SUBSTANCE OF ANAPHYLAXIS
Authors: BURKA J.F. , FLOWER R.J. 
Published: July 2012

Slow‐reacting substance of anaphylaxis (SRS‐A) was released in the peritoneum of passively sensitized rats challenged with ovalbumin and from rat isolated peritoneal cells stimulated with calcium ionophore A23187.
Both monocytes (macrophages) and mast cells appear to be involved in the synthesis and release of SRS‐A.
The immunological release of SRS‐A in vivo is enhanced by indomethacin and inhibited by dexamethasone, mepacrine, 1‐phenyl‐3‐pyrazolidone (1‐P‐3‐P), and methylimidazole.
SRS‐A release induced by A23187 in vitro is inhibited by dexamethasone, indomethacin, 1‐P‐3‐P, eicosatetraynoic acid (ETA) and 15‐hydroperoxy arachidonic acid. The inhibition induced by dexamethasone, indomethacin and 1‐P‐3‐P is reduced by an increase in the calcium concentration from 1 mm to 5 mm, whereas the inhibition induced by ETA is increased.
The results suggest that a lipoxygenase is important in the synthesis and release by SRS‐A.
LOCALIZATION OF SENSITIVE SITES TO TAURINE, γ‐AMINOBUTYRIC ACID, GLYCINE AND β‐ALANINE IN THE MOLECULAR LAYER OF GUINEA‐PIG CEREBELLAR SLICES
Authors: OKAMOTO KOICHI , SAKAI YUTAKA 
Published: July 2012

The localization, in the molecular layer of guinea‐pig cerebellar slices, of the sites most sensitive to iontophoretically applied taurine, γ‐aminobutyric acid (GABA), glycine and β‐alanine was investigated.
The most sensitive sites were located (expressed as the distance from the Purkinje cell body to the pial surface): 0 μm, 60 μm and 220 μm for taurine; 0 μm and 180 μm for GABA; 80 μm and 200 μm for glycine, and 80 μm, 180 μm and 300 μm for β‐alanine.
The sensitive site (at 0 μm) to GABA was considered to represent the basket synapses on the Purkinje cell soma, while the sites (60 to 80 μm and 200 to 300 μm) for taurine, glycine and β‐alanine were tentatively assigned to the synapses of the stellate neurones on the Purkinje cell dendrites.
Inhibitory actions of all four amino acids tested at the most sensitive sites were antagonized by both picrotoxin and strychnine.
The possibility that taurine might be the neurotransmitter of the stellate neurones in guinea‐pig cerebellum is discussed.
AN in vitro STUDY OF VARIOUS DRUGS ON CENTRAL AND PERIPHERAL AIRWAYS OF THE RAT: A COMPARISON WITH HUMAN AIRWAYS
Authors: LULICH K.M. , PATERSON J.W. 
Published: July 2012

The effect of histamine and other drugs on the central and peripheral airways of the rat was studied by applying them directly to isolated tracheal and lung strip preparations. These effects were then compared with those observed on human isolated bronchial muscle preparations.
Acetylcholine and 5‐hydroxytryptamine (5‐HT) both contracted the lung strip and trachea of the rat, and both were more potent on the trachea than the lung strip.
Histamine and prostaglandins E2 (PGE2) or F2γ (PGF2γ) produced no effect on either the lung strip or trachea of the rat.
On the human isolated bronchial preparation, in contrast to the rat airways, both histamine and PGF2γ produced marked concentration‐dependent contractions and 5‐HT either produced no response or a slight relaxation.
In view of these results, the use of anaphylactic bronchoconstriction in the rat as a model for the study of asthma in man is questioned.
INHIBITION OF VASOPRESSIN RELEASE TO CAROTID OCCLUSION BY γ‐AMINOBUTYRIC ACID AND GLYCINE
Authors: FELDBERG W. , SILVA M. ROCHA E 
Published: July 2012

In cats anaesthetized with pentobarbitone sodium or chloralose, the amino acids, γ‐aminobutyric acid (GABA) and glycine, were applied to the ventral surface of the brain stem through paired Perspex rings placed across the medulla.
Applied to a region situated at the transition between medulla and cord, both amino acids greatly attenuated and even abolished the vasopressin release in response to carotid occlusion. Glycine was about 100 times more potent than GABA and effective in a concentration of 0.1 mg/ml. The pressor response to carotid occlusion was not affected.
Applied to a region situated 5 to 6 mm more rostrally, the amino acids did not affect vasopressin release but in strong concentrations, greatly attenuated the pressor response to carotid occlusion.
The two responses to carotid occlusion, vasopressin release and the pressor response, can thus be influenced independently.
It is concluded that the pathways carrying afferent impulses from the baroreceptors in the carotid sinus reach the ventral surface of the brain stem at two regions. At both, synaptic transmission can be blocked by the application of an inhibitory amino acid and thus prevent either the release of vasopressin at the caudal site, or the increase of vasomotor tone at the rostral site.
ANTAGONISM OF VASODEPRESSOR AND GASTRIC SECRETORY RESPONSES TO HISTAMINE BY THE H2‐RECEPTOR ANTAGONISTS, RANITIDINE AND CIMETIDINE, IN THE ANAESTHETIZED DOG
Authors: DALY M.J. , HUMPHRAY JANET M. , STABLES R. 
Published: July 2012

The new H2‐receptor antagonist, ranitidine, has been compared with cimetidine as an inhibitor of gastric acid secretion in the anaesthetized dog.
Both ranitidine and cimetidine given intravenously inhibited histamine‐induced gastric secretion in a dose‐related manner. Ranitidine was 4.2 times more potent than cimetidine when given as an intravenous infusion and 9.6 times more potent as an intravenous bolus dose.
In a separate series of experiments, ranitidine was compared with cimetidine as an antagonist of vasodepressor responses to histamine. Mepyramine alone displaced the histamine dose‐response curve to the right. After a maximally effective dose of mepyramine, further displacement could be achieved with ranitidine and cimetidine, ranitidine being 19.2 times more potent than cimetidine.
Ranitidine alone had no effect on vasodepressor response curves to histamine, acetylcholine or (−)‐isoprenaline or on vasopressor response curves to phenylephrine.
These results indicate that displacement of the histamine dose‐response curve after mepyramine blockade by ranitidine and cimetidine is due to selective H2‐receptor antagonism.
FURTHER EVIDENCE FOR THE INVOLVEMENT OF Na+CHANNELS IN THE RELEASE OF ADRENAL CATECHOLAMINE: THE EFFECT OF SCORPION VENOM AND GRAYANOTOXIN I
Authors: ITO S. , NAKAZATO Y. , OHGA A. 
Published: July 2012

The effects of venom from the scorpion, Leiurus quinquestriatus, and grayanotoxin I on catecholamine secretion were studied in the perfused adrenal glands of guinea‐pig.
Scorpion venom (0.1 to 10 μg/ml) caused a dose‐dependent increase in catecholamine output. The response to the venom was partially inhibited by atropine (0.5 mm) plus hexamethonium (1 mm). The dose‐response curve was shifted to the right in the presence of these blocking agents.
Grayanotoxin I (0.1 to 0.5 mm) caused a dose‐dependent increase in catecholamine output which was significantly reduced by atropine (0.5 mm) plus hexamethonium (1 mm). However, when grayanotoxin I (0.1 mm) was applied together with scorpion venom (0.1 μg/ml, a concentration which alone, was almost ineffective) the maximum catecholamine output was reached even in the presence of atropine plus hexamethonium.
Tetrodotoxin (0.1 or 0.2 μm) reversibly inhibited the secretory responses induced by scorpion venom (10 μg/ml) and grayanotoxin I (0.1 mm) plus scorpion venom (0.1 μg/ml).
Scorpion venom and grayanotoxin I plus scorpion venom did not cause catecholamine secretion in the absence of extracellular Na+or Ca2+ions. However, the secretory response was restored by reintroduction of Na+or Ca2+ions.
It is suggested that both scorpion venom and grayanotoxin I activate Na+channels on the chromaffin cell and result in catecholamine secretion.
EFFECTS OF NERVE STIMULATION AND OF ADMINISTRATION OF NORADRENALINE OR POTASSIUM CHLORIDE UPON THE RELEASE OF PROSTAGLANDINS I2, E2 AND F2α FROM THE PERFUSED MESENTERIC ARTERIAL BED OF THE RABBIT
Authors: PIPILI EVA , POYSER N.L. 
Published: July 2012

The release of prostaglandin I2 (PGI2), PGE2 and PGF2α from the perfused mesenteric arterial bed of the rabbit was examined at rest, following nerve stimulation and following noradrenaline (NA) or potassium chloride (KCl) administration.
Stimulation of adrenergic nerves at 10 Hz caused a significant increase in the release of both PGI2, (assayed in terms of 6‐oxo‐PGF1α) and PGE2 but a significant decrease in the release of PGF2α.
Exogenous Na (2 μg) increased the output of PGI2 and PGE2 but left the output of PGF2α unaffected.
KCl (15 mg) significantly increased the output of PGF2α but left the output of PGI2 unaffected.
It is concluded that PGI2 and PGE2 output from the mesenteric arterial bed of the rabbit increases following stimulation of adrenoceptors. The sympathetic nervous system may therefore modulate PGI2/platelet interaction.
Prostaglandins released from the blood vessels by sympathetic nerve stimulation may also modulate adrenergic transmission to the blood vessels.
ALTERATION OF SMOOTH MUSCLE CONTRACTILITY AFTER MUSCARINIC AGONIST‐INDUCED K+ LOSS
Authors: JAMES‐KRACKE MARILYN R. , ROUFOGALIS BASIL D. 
Published: July 2012

After stimulation of the longitudinal smooth muscle of the guinea‐pig ileum by an optimal dose (2times10−7 m) of a muscarinic agent, cis‐2‐methyl‐4‐dimethylaminomethyl‐1,3‐dioxolane methiodide (CD), the muscles failed to regain their normal spontaneous activity for 20 to 30 min. During the recovery period, subsequent contractions induced by either CD or 60 mm KCl were altered, particularly when only short times (15 min or less) were allowed between exposures.
Altered responses to CD had depressed phasic but increased tonic tensions and were characteristic of responses induced by lower doses of CD. The altered responsiveness probably represented an early phase of muscle ‘desensitization’.
In contrast to muscarinic stimulation, the smooth muscles gave identical responses after repeated stimulation by 60 mm KCl, even when only 2 min were allowed between exposures.
Whereas K+ levels increased in muscles exposed to 60 mm KCl, they decreased during contractions to CD. The K+ levels remained low until the muscles recoverd their normal responsiveness.
Increasing the extracellular K+ concentration (5 to 13 mm) hastened the recovery of the muscle responsiveness after CD, whereas lowering external K+ concentration to 1.35 mm or the addition of ouabain (5times10−7 m) delayed the recovery. The results suggested that the Na+,K+‐pump is rate‐limiting in the recovery of the normal ionic balance of the muscles after stimulation by muscarinic agonists.
THE EFFECT OF FENFLURAMINE ON THE MICROSTRUCTURE OF FEEDING AND DRINKING IN THE RAT
Authors: BURTON M.J. , COOPER S.J. , POPPLEWELL D.A. 
Published: July 2012

The effects of three doses of fenfluramine on feeding and drinking in the rat were examined.
Feeding and drinking were subdivided into meals and bouts, and the changes in feeding/drinking were expressed in terms of meal/bout frequency, meal/bout size, meal/bout length, and eating/drinking rate.
The changes in these parameters were examined over different time periods after the injection.
Significant changes in the distribution of inter‐response intervals within meals were found in time period 1 with 5 mg/kg and 10 mg/kg doses of fenfluramine. Videotape and computer analysis showed that the changes in inter‐response interval histograms differed significantly from those seen in normal animals approaching satiety. Drinking parameters also changed.
Compensatory increases in feeding were observed in time period 4 with the 10 mg/kg dose.
The difficulties in designing and interpreting experiments in feeding are discussed, and the action of fenfluramine as an anorectic drug is considered.
MECHANICAL AND ELECTROPHYSIOLOGICAL EFFECTS OF SEA ANEMONE (Anemonia sulcata) TOXINS ON RAT INNERVATED AND DENERVATED SKELETAL MUSCLE
Authors: ALSEN C. , HARRIS J.B. , TESSERAUX I. 
Published: July 2012

Some effects of the sea‐anemone toxin ATX‐II on mammalian nerve‐muscle preparations have been described
When ATX‐II (10−8‐10−6 m) was applied to rat hemidiaphragm preparations, both directly and indirectly generated twitch responses were potentiated and prolonged. At the same time the resting tension of the preparations increased
The increase in resting tension caused by ATX‐II in innervated muscles was not prevented by curarization, but was reversed by exposure to tetrodotoxin. The increase in denervated muscles was not completely reversed by tetrodotoxin
At concentrations exceeding 1 × 10−7 M, ATX‐II caused a sodium‐dependent depolarization of both normal and denervated muscles. The depolarization of the denervated muscles was only partially reversed by tetrodotoxin
In the presence of ATX‐II repetitive endplate potentials (e.p.ps) were evoked by single shocks to the motor nerves in many fibres, and in those in which a single e.p.p. was still observed, the quantum content (m) was increased. Miniature e.p.p. frequency was not increased by ATX‐II, even when muscle fibres were depolarized by 30 mV
The indirectly and directly elicited action potentials of normal and denervated muscle fibres were much prolonged by ATX‐II. The action potentials remained sodium‐dependent. The sodium‐dependent tetrodotoxin‐resistant action potential of the denervated muscle fibre was also prolonged by ATX‐II. 7 It is concluded that ATX‐II both activates, and delays inactivation of, sodium channels in mammalian skeletal muscle fibres, probably by interacting with the channel ‘gate’.
THE ACQUISITION OF RESPONDING WITH CONDITIONED REINFORCEMENT: EFFECTS OF COCAINE, (+)‐AMPHETAMINE AND PIPRADROL
Authors: BENINGER RICHARD J. , HANSON DALE R. , PHILLIPS ANTHONY G. 
Published: July 2012

A procedure for examining the acquisition of a lever‐pressing operant with conditioned reinforcement was used to compare the effects of three psychomotor stimulants
Hungry rats were trained to associate an auditory tone (i.e., conditioned reinforcer) with food. Preference for the tone was then measured after treatment with pipradol (5, 10, 15 mg/kg), cocaine (1, 5, 10mg/kg)or(+)‐amphetamine(0.5, 1.5, 5.0 mg/kg)
In agreement with previous data, 10 mg/kg of pipradrol enhanced the effect of conditioned reinforcement whereas animals treated with any of the doses of (+)‐amphetamine showed no effect
Rats treated with cocaine (1 or 5 mg/kg) showed an effect of conditioned reinforcement but the effect was not significantly greater than in controls
The present data suggest important differences in enhancement of responding for conditioned reinforcement by various drugs in the psychomotor stimulant class. These differences in turn may be related to the pharmacological actions of these compounds on release of catecholamines from different storage pools.
In vivo AND in vitro EFFECTS OF ENDOTOXIN ON PROSTAGLANDIN RELEASE FROM RAT LUNG
Authors: FEUERSTEIN NILI , RAMWELL PETER W. 
Published: July 2012

The release of prostaglandins (PGE2, PGF2α, PGI2) and thromboxane A2 (T×A2) from rat lung exposed to E. coli endotoxin, in vivo ox in vitro has been studied.
Lung strips of endotoxin‐treated rats demonstrated a preferential increase of T×A2 and PGF2α and a decrease in the ratio PGI2/T×A2.
These data suggest that changes in the proportions of arachidonic acid metabolites might play a role in the pulmonary pathophysiology during endotoxin shock.
Incubation of lung strips with endotoxin in vitro failed to stimulate prostaglandin release; paradoxically, it suppressed both the spontaneous and the ionophore‐induced prostaglandin release.
These findings suggest that the increase in prostaglandin release by the lung following endotoxin administration in vivo is probably mediated by factor(s) generated in endotoxaemia and is not due to a direct action of endotoxin on the lung tissue.
INVOLVEMENT OF THE ADRENAL GLANDS IN THE HYPOTENSIVE RESPONSE TO BROMOCRIPTINE IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: HAMILTON T.C. 
Published: July 2012

The dopamine agonist, bromocriptine, produced a hypotensive response following oral administration to conscious normotensive and spontaneously hypertensive (SH‐) rats.In SH‐rats the dose‐related falls in blood pressure to bromocriptine, 3 to 30 mg/kg orally or intraperitoneally, were biphasic, an initial fall at 1 h being followed by some recovery at 2 h and a subsequent fall in blood pressure at 4 and 6 h.The dopamine antagonists, metoclopramide, sulpiride, haloperidol and pimozide, had little or no effect on the hypotensive response to bromocriptine, 10 mg/kg orally, in SH‐rats.Pretreatment with α‐methyl‐p‐tyrosine augmented the hypotensive response to bromocriptine, 10 mg/kg orally, in SH‐rats.In adrenal demedullated SH‐rats, the hypotensive response to bromocriptine, 3 to 30 mg/kg orally, was abolished.In SH‐rats the hypotensive response to bromocriptine, 10 mg/kg orally, was prevented by the β‐adrenoceptor blocking drugs, propranolol and oxprenolol, but was unaffected by (+)‐propranolol and by the cardio‐selective β‐adrenoceptor blocking drug, atenolol.In SH‐rats pretreated with bromocriptine, 10 mg/kg orally, and then anaesthetized, the pressor responses to low doses of intravenous adrenaline were reversed to depressor, indicating that bromocriptine possesses α‐adrenoceptor blocking activity.The results suggest that the hypotensive response to bromocriptine in conscious SH‐rats is mediated by adrenaline released from the adrenal medullae which, in the presence of α‐adrenoceptor blockade, stimulates vascular β‐adrenoceptors producing vasodilatation.
COMPARISON OF THE ACTIONS OF U‐46619, A PROSTAGLANDIN H2‐ANALOGUE, WITH THOSE OF PROSTAGLANDIN H2 AND THROMBOXANE A2 ON SOME ISOLATED SMOOTH MUSCLE PREPARATIONS
Authors: COLEMAN R.A. , HUMPHREY P.P.A. , KENNEDY I. , LEVY G.P. , LUMLEY P. 
Published: July 2012

The actions of the prostaglandin H2 (PGH2) analogue, U‐46619, have been compared with those of PGH2 and thromboxane A2 (TxA2) on a range of isolated smooth muscle preparations in a superfusion cascade system.
U‐46619 was a potent agonist on guinea‐pig lung strip, dog saphenous vein and rat and rabbit aortae. In contrast, U‐46619 was weak or inactive on guinea‐pig ileum and fundic strip, cat trachea and dog and cat iris sphincter muscles, preparations on which either PGE2 or PGF2α was the most potent agonist studied.
PGH2 was active on all of the preparations and displayed little selectivity. On some of the preparations, the actions of PGH2 may have been mediated indirectly by conversion to other prostanoids.
In contrast, TxA2 displayed the same pattern of selectivity as U‐46619, being a potent agonist on the lung strip and vascular preparations but weak or inactive on the others.
It is suggested that U‐46619 is a selective TxA2‐mimetic and that it should therefore be a valuable tool in the study of the actions of TxA2
EFFECTS ON RABBIT NODAL, ATRIAL, VENTRICULAR AND PURKINJE CELL POTENTIALS OF A NEW ANTIARRHYTHMIC DRUG, CIBENZOLINE, WHICH PROTECTS AGAINST ACTION POTENTIAL SHORTENING IN HYPOXIA
Authors: MILLAR J.S. , WILLIAMS E.M. VAUGHAN 
Published: July 2012

The effects of cibenzoline (UP 339–01), a new anti‐arrhythmic drug, have been investigated in various cardiac tissues.
UP 339–01 produced a bradycardia, due partly to prolongation of the intracellularly recorded sinus node action potential duration (APD) and partly to depression of the maximum rate of depolarization (MRD). The slope of the slow diastolic depolarization was not significantly reduced.
UP 339–01 was not a β‐adrenoceptor antagonist.
UP 339–01 was negatively inotropic, and shifted the relation between [Ca2+]o and force of contractions to the right, and increased A‐H conduction time. It was concluded that UP 339–01 restricted slow inward current.
In all cardiac tissues depolarized by fast inward current, UP 339–01 caused a reduction in MRD and conduction velocity. The reduction was similar in atrial muscle, His and terminal Purkinje fibres, but in papillary muscle the effect was about half as great. On desheathed frog nerve UP 339–01 had a local anaesthetic potency slightly greater than that of procaine.
APD was significantly prolonged in a dose‐related manner in ventricular muscle but to a lesser extent in the bundle of His and atrial tissue. In terminal Purkinje fibres APD50 and APD90 were unaltered, but the transient outward current (‘notch’) was abolished, resulting in a lengthening of APD20.
The effective and functional refractory periods of the A—V node and right bundle branch were both lengthened by UP 339–01 in a dose‐related manner, and the difference between them was greatly increased.
UP 339–01 (2.63 μm) completely prevented the shortening of APD90 induced by hypoxia, and the shortening of APD50 and APD20 was much attenuated. There was no protection against hypoxic depression of contractions.
It was concluded that UP 339–01 is a highly active class 1 anti‐arrhythmic agent with additional class 3 and 4 properties.
THE ACTION OF PORCINE GLUCAGON ON THE MOTILITY OF THE CANINE DUODENUM AND JEJUNUM
Authors: EVANS D.F. , FOSTER G.E. , HARDCASTLE J.D. , JOHNSON F. , WRIGHT J.W. 
Published: July 2012

Intravenous bolus doses of porcine glucagon of 0.001 −0.05 mg kg−1 caused intense stimulation of the duodenum and jejunum of the dog.
Intravenous infusion of porcine glucagon at 0.025 −0.05 mg kg−1 h−1 caused similar stimulation. In both cases the stimulation was phasic in nature.
Stimulation of the duodenum and jejunum following glucagon was accompanied by a decrease in frequency of the intestinal basic electrical rhythm (BER). No change was seen in the intervals between successive periods of phase III motor activity.
INHIBITION OF ADRENALINE‐INDUCED PLATELET AGGREGATION BY THE α‐ADRENOCEPTOR BLOCKING DRUG BENEXTRAMINE
Authors: BELLEAU B. , BENFEY B.G. , MELCHIORRE C. , MONTAMBAULT M. 
Published: July 2012

The activity of the irreversible α‐adrenoceptor blocking drug, benextramine, was determined in human platelets.
Compared to its postsynaptic and presynaptic α‐adrenoceptor blocking potency, benextramine had a very low potency as an antagonist of adrenaline‐induced platelet aggregation.
The results confirm the previous observation with the irreversible α‐adrenoceptor blocking drug, phenoxybenzamine, that platelet α‐adrenoceptors differ from postsynaptic and presynaptic α‐adrenoceptors.
EFFECTS OF H2‐RECEPTOR ANTAGONISTS AND ANTICHOLINOCEPTOR DRUGS ON GASTRIC AND SALIVARY SECRETION INDUCED BY BETHANECHOL IN THE ANAESTHETIZED DOG
Authors: DALY M.J. , HUMPHRAY JANET M. , STABLES R. 
Published: July 2012

The H2‐receptor antagonists, ranitidine and cimetidine, have been compared with, atropine and pirenzepine for their effects on gastric acid output, and on salivary secretion from the left parotid gland in the anaesthetized dog. Gastric and salivary secretions were elicited by intravenous infusion of bethanechol.
Atropine (0.3–1 Mg μg/kg) or pirenzepine (3–10 μg/kg) reduced both gastric and salivary secretions, pirenzepine showing little evidence of any selectivity for gastric secretion.
The H2‐receptor antagonists, ranitidine (30–1000 μg/kg) and cimetidine (100–3000 μg/kg), selectively inhibited gastric secretion and even at relatively high dose levels did not alter salivary volume.