bluuebunny/crossref_metadata_2025_split huggingface dataset:
PROSTAGLANDINS AND THE CONTRACTILE ACTION OF BRADY‐KININ ON THE LONGITUDINAL MUSCLE OF RAT ISOLATED ILEUM
Authors: WALKER R. , WILSON KEITH A. 
Published: July 2012

The effect of the prostaglandin synthesis inhibitors aspirin and indomethacin (Ind) was investigated upon contractions of the perfused isolated terminal ileum of the rat to bradykinin (Bk) or potassium chloride (KC1). The release of a prostaglandin‐like substance (PGLS) from the ileum was simultaneously assayed on the rat fundus strip (RFS).
Aspirin (610 μm) or Ind (28 μm) reduced contractions of the ileum to Bk perfused over the mucosal surface but not to Bk perfused over the serosal surface.
After perfusion of either ileal surface the effluent potentiated the contractions of the RFS to Bk. No potentiation was observed in the presence of either Ind or aspirin.
Contractions of the RFS to Bk were potentiated by prostaglandin E2 (PGE2) (0.7 × 10−12 m and 1.4 × 10−12 m) but not by either a higher (2.8 × 10−12 m) or a lower (0.35 × 10−12 m) concentration of PGE2. No potentiation was observed with prostaglandin F2α (PGF2α) at the concentrations studied.
Only the contractile action of Bk acting on the mucosal surface of the rat isolated perfused ileum seems to involve prostaglandin synthesis.
SELECTIVE ANTAGONISM BY BENZODIAZEPINES OF NEURONAL RESPONSES TO EXCITATORY AMINO ACIDS IN THE CEREBRAL CORTEX
Authors: ASSUMPÇÃO J.A. , BERNARDI N. , BROWN J. , STONE T.W. 
Published: July 2012

The recently discovered benzodiazepine receptor exists in high concentration in the cerebral cortex. We have, therefore, examined the effects of diazepam and chlordiazepoxide on cortical neurone responses to excitatory and inhibitory amino acids and acetylcholine, in the cortex of rats anaesthetized with urethane.
Chlordiazepoxide applied by microiontophoresis reduced the responses to glutamate and aspartate but acetylcholine responses were unaffected on most cells even by much higher doses of benzodiazepine. γ‐Aminobutyric acid (GABA) and taurine responses were unaffected on most cells, but were reduced on 4 of 25 units. After intravenous diazepam, responses to GABA and taurine were reduced on 3 cells and unchanged on 11.
On Purkinje cells in the cerebellum a number of cells (5 of 16) exhibited a substantial increase in responses to GABA and taurine following intravenous or iontophoretic application of benzodiazepines.
It is suggested that the highly selective reduction of excitatory amino acid responses in the cerebral cortex may be of particular relevance to the behavioural effects of benzodiazepines.
PHARMACOLOGICAL EFFECTS OF PHOSPHATIDYLSERINE LIPOSOMES: THE ROLE OF LYSOPHOSPHATIDYLSERINE
Authors: BIGON E. , BOARATO E. , BRUNI A. , LEON A. , TOFFANO G. 
Published: July 2012

Unique among the phospholipids, phosphatidylserine depresses brain energy metabolism when injected intravenously into mice in the form of sonicated liposomes. The possibility that this effect results from a metabolic transformation of phosphatidylserine is examined in this paper.
A strong enhancement of the phosphatidylserine effect is induced by the incubation of liposomes with rat serum. Similar phosphatidylserine activation is observed after the incubation of the phospholipid with purified phospholipase A2 from pancreas. In both cases phosphatidylserine is split into the deacylated derivative, lysophosphatidylserine.
Lysophosphatidylserine reproduces with greater efficacy the effect of phosphatidylserine on brain energy metabolism. Other lysophospholipids are not effective.
It is concluded that the pharmacological effects of phosphatidylserine liposomes is due to the generation of lysophosphatidylserine.
EFFECTS OF A COMBINED OESTROGEN‐PROGESTIN PREPARATION ON GASTRIC ACID AND PEPSIN SECRETION, SERUM GASTRIN CONCENTRATION AND BILIARY SECRETION OF BILE ACIDS, PHOSPHOLIPIDS, AND CHOLESTEROL IN THE CAT
Authors: HIRST B.H. , LUND P. KAY , REED THE LATE J.D. , SANDERS D.J. , SHAW B. , TAYLOR W. 
Published: July 2012

Daily ethinyloestradiol (50μg) and norethisterone acetate (1 mg) treatment (Minovlar) was investigated on gastric acid and pepsin secretion, and fasting serum gastrin concentration in six conscious female cats prepared with chronic gastric fistulae. The effect on biliary secretion of bile acids, phospholipids, and cholesterol was investigated in three conscious female cats prepared with chronic gastric and intestinal fistulae, and cholecystectomy.
Treatment for 49 days did not alter the gastric acid or pepsin response to either intravenous pentagastrin infusions or a food stimulus. The fasting serum gastrin concentration remained unaltered throughout the study.
Treatment for 18 days did not alter the percentage concentration of cholesterol in the bile, but reduced the percentage concentration of phospholipid. This was mirrored by a rise in the percentage concentration of bile acids in the bile. These trends were quickly reversed on cessation of treatment.
There was no sign of cholestasis associated with the treatment. Intestinal flow remained constant throughout the study, there was no lithocholic acid or other abnormal bile acids detectable in any samples, and there was no change in serum aspartate aminotransferase concentration.
The results suggest that in female cats, treatment with a combined oestrogen‐progestin preparation does not exert any beneficial effects on the aetiology of peptic ulceration through the reduction of acid or pepsin secretion, or the lowering of serum gastrin concentration. The preparation shows a tendency to produce more lithogenic bile, and this may partly explain the greater incidence of gall stones in women on the contraceptive pill.
POSSIBLE MECHANISMS OF ACTION OF Gymnodinium breve TOXIN AT THE MAMMALIAN NEUROMUSCULAR JUNCTION
Authors: SHINNICK‐GALLAGHER PATRICIA 
Published: July 2012

The mechanism of action of a crude fraction of Gymnodinium breve toxin (GBTX) was investigated by intracellular recording techniques in the rat phrenic nerve diaphragm preparation.
GBTX (2 μg/ml) decreased the input resistance of the muscle membrane concomitantly with a depolarization of the resting membrane potential.
A low sodium solution reversed or prevented a GBTX‐induced membrane depolarization.
Tetrodotoxin (TTX) antagonized a GBTX‐induced increase in miniature endplate potential (m.e.p.p.) frequency and repolarized a GBTX‐depolarized membrane. Pretreatment with TTX prevented GBTX effects.
GBTX reversibly reduced depolarizations produced by bath applied acetylcholine (ACh). The membrane depolarization was not responsible for the depression of ACh responses.
These findings suggest that GBTX increases m.e.p.p. frequency and depolarizes the resting membrane potential by increasing sodium permeability. The reduction of ACh‐induced depolarizations suggests that GBTX may be acting at some site on the ACh receptor.
PHENOBARBITONE INTERACTION WITH ORAL CONTRACEPTIVE STEROIDS IN THE RABBIT AND RAT
Authors: BACK D.J. , BRECKENRIDGE A.M. , CRAWFORD FRANCESCA E. , ORME M.L'E. , ROWE P.H. 
Published: July 2012

The effect of phenobarbitone on the single dose pharmacokinetics of the synthetic steroids, ethinyloestradiol (EE2) and norethisterone, has been studied in the rabbit and rat.
EE2 is subject to an extensive first pass effect (96%). The plasma clearance of EE2 approaches total hepatic blood flow. It is suggested that a secondary peak in EE2 plasma concentration time curves at 5 h is due to enterohepatic recycling. Phenobarbitone had no effect on plasma EE2 concentrations following intravenous administration and produced a variable decrease after oral administration.
In phenobarbitone‐treated rabbits, following intravenous administration of norethisterone there was no significant change in the area under the curve (AUC) compared to controls. In contrast, following oral administration of norethisterone to treated rabbits, the AUC was 20% and the peak plasma concentration 17% of that in controls.
The data in rabbits are consistent with drugs which are highly extracted by the liver.
In rats, phenobarbitone had no effect on plasma norethisterone concentrations following intravenous or hepatic portal (bolus) administration, but caused a decrease in systemic availability after both infusion into the portal vein (over a period of 5 min) and oral administration.
It is concluded that the rate of delivery of norethisterone to the liver is important in determining whether or not enzyme induction will cause an increased first pass effect.
Phenobarbitone caused an increase in conjugation of norethisterone in the gastrointestinal tract of rats.
COMPARATIVE STUDY OF THE EFFECTS OF 4‐AMINOPYRIDINE AND TETRAETHYLAMMONIUM ON NEURO‐EFFECTOR TRANSMISSION IN THE GUINEA‐PIG VAS DEFERENS
Authors: ITO YUSHI , KORENAGA SUSUMU , TAJIMA KIKUO 
Published: July 2012

Effects of 4‐aminopyridine (4‐AP) and tetraethylammonium (TEA) on the neuro‐effector junction of the guinea‐pig vas deferens were investigated by microelectrode and double sucrose gap techniques.
4‐AP (0.05 to 0.5 mm) or TEA (0.5 to 1 mm) did not alter the membrane potential, or the membrane input resistance of the smooth muscle cell.
The amplitude and frequency of the miniature junction potentials (m.e.j.ps) were not modified by treatment with 4‐AP (0.05 to 0.5 mm) or TEA (1 mm).
4‐AP (1 mm) increased the membrane input resistance, enhanced the spike amplitude of the smooth muscle cells and thereby augmented the amplitude of twitch contraction.
4‐AP (0.05 to 0.5 mm) or TEA (1 mm) markedly increased the amplitude of excitatory junction potentials (e.j.ps), but the facilitation phenomena produced by repetitive stimulation were not affected.
The duration of the extracellularly recorded action potential from the small nerve bundle was prolonged by 4‐AP (0.5 mm).
The amplitude of the e.j.p. was dependent on the external concentration of calcium. A straight line was produced when the amplitude of the e.j.p. and [Ca]o was plotted on a double log scale. Application of 4‐AP resulted in a parallel shift of this line to the left.
These results indicate that 4‐AP (0.05 to 0.5 mm) and TEA (0.5 to 1.0 mm) prolonged the action potential generated from the sympathetic nerve terminal thus enhancing the amplitude of the e.j.p. due to an increase in the Ca‐influx. However, in the concentrations used, these compounds did not modify the Ca‐mobilization in the nerve terminal or the postsynaptic membrane during the resting state.
THE EFFECT OF CONDITIONS INFLUENCING ENDOGENOUS PROSTAGLANDINS ON THE ACTIVITY OF Δ′‐TETRAHYDROCANNABINOL IN MICE
Authors: FAIRBAIRN J.W. , PICKENS JOAN T. 
Published: July 2012

The cataleptic effect of Δ′‐tetrahydrocannabinol (THC) depends upon the availability of the precursors of prostaglandins and the response is reduced in mice maintained on a diet deficient in arachidonic acid (AA) and restored by exogenous AA given intraperitoneally, or by feeding a normal diet.
In yeast‐induced fever, which is accompanied by an increase in the synthesis of prostaglandins, THC shows an enhanced cataleptic effect.
Exposure to cold which results in depletion of prostaglandins reduces the effect of THC.
PROSTACYCLIN‐DEPENDENT ACTIVATION OF ADENYLATE CYCLASE IN A NEURONAL SOMATIC CELL HYBRID: PROSTANOID STRUCTURE‐ACTIVITY RELATIONSHIPS
Authors: BLAIR I.A. , HENSBY C.N. , MacDERMOT J. 
Published: July 2012

Prostacyclin activates adenylate cyclase of the NCB‐20 neuronal hybrid cell line.
There is a guanosine 5′‐triphosphate requirement for the activation of adenylate cyclase by 5,6β‐dihydroprostacyclin (a stable analogue of prostacyclin).
Steady‐state kinetic analysis of the activation of adenylate cyclase by 5,6β‐dihydroprostacyclin suggests a simple non‐cooperative bimolecular interaction between the ligand and a single receptor population.
Structure‐activity relationships of selected prostanoids elucidated certain functional requirements for activation of adenylate cyclase.
STUDIES ON THE MECHANISM OF ACTION OF VARIOUS VASODILATORS
Authors: GAGNON G. , REGOLI D. , RIOUX F. 
Published: July 2012

The vascular relaxant effects of histamine, adenosine, isoprenaline nitroglycerine, papaverine and 3‐isobutyl‐1‐methylxanthine (IBMX) were assessed individually, in strips of rabbit renal artery moderately contracted with noradrenaline (NA) in the absence or presence of phosphodiesterase inhibitors (papaverine and IBMX) or verapamil, a Ca2+ antagonist.
The vasodilator effect of histamine was potentiated by papaverine (6.1 × 10−7 m) and IBMX (4.4 × 10−5 m) but inhibited dose‐dependently by verapamil (5.1 and 51.0 × 10−7 m).
Adenosine‐induced vascular relaxations were greatly increased in the presence of papaverine (6.1 × 10−7 m) but significantly reduced in the presence of IBMX (4.4 × 10−5 m) or verapamil (5.1 and 51.0 × 10−7 m).
The vasodilatation produced by isoprenaline was increased in the presence of IBMX (4.4 × 10−5 m) or papaverine (6.1 × 10−7 m), but inhibited by verapamil (5.1 and 51.0 × 10−7 m).
The vascular relaxant effects of nitroglycerine and papaverine were inhibited in the presence of IBMX (4.4 × −5 m) or verapamil (5.1 and 51.0 × 10−7 m). Papaverine (6.1 × 10−7 m) also antagonized nitroglycerine‐induced vascular relaxation.
The vasodilator effect of IBMX was greatly reduced in the presence of papaverine (6.1 × 10−7 m) or verapamil (5.1 and 51.0 × 10−7 m).
The vascular relaxant effect of verapamil was reduced proportionally by raising the extracellular Ca2+ concentration from 1.25 to 5.0 mm while those elicited by histamine, adenosine, isoprenaline, nitroglycerine, papaverine and IBMX were not modified by this procedure.
These results were taken as an indication that several vasodilators (e.g. histamine, adenosine, isoprenaline, nitroglycerine, papaverine and IBMX), but not a Ca2+ antagonist such as verapamil, produce a fraction of their vasodilator effects by promoting Ca2+ extrusion from and/or Ca2+ sequestration into the vascular smooth muscle cells, via a cyclic adenosine 3′,5′‐monophosphate‐dependent mechanism.
CENTRAL RESPIRATORY AND CIRCULATORY EFFECTS OF Gymnodinium breve TOXIN IN ANAESTHETIZED CATS
Authors: BORISON HERBERT L. , ELLIS SYDNEY , McCARTHY LAWRENCE E. 
Published: July 2012

In cats anaesthetized with pentobarbitone, observations were made on respiration, spontaneous and evoked diaphragmatic electromyograms, blood pressure, heart rate, indirectly‐induced contractions of the anterior tibialis muscle and nictitating membrane, and electrical excitability of the inspiratory centre in the medulla oblongata.
Gymnodinium breve toxin (GBTX) was administered intravenously, intra‐arterially to the brain, and intracerebroventricularly. Physiological effects were recorded while alveolar Pco2 was controlled at a constant level except when changes in gas tension were made in order to measure C02‐ventilatory responsiveness.
Adequate doses of GBTX given intravenously by bolus injection elicited a non‐tachyphylactic reflex response triad of apnoea, hypotension and bradycardia mediated by the vagus nerves independently of arterial baroreceptor and chemoreceptor innervation.
After vagotomy, additional amounts of GBTX (i.v.) resulted in apneustic breathing, hypertension and tachycardia. The cardiovascular effects were abolished by ganglionic blockade with hexamethonium.
Smaller doses of GBTX were required intra‐arterially and intracerebroventricularly than by the intravenous route of injection to produce respiratory irregularity and cardiovascular hyperactivity.
Evoked motor responses, electrical excitability of the medulla oblongata and CO2‐ventilatory responsiveness were largely spared even though GBTX caused marked disturbances in respiratory rhythmicity and cardiovascular functions.
It is concluded that GBTX acts reflexly on vagally innervated receptors to evoke a Bezold‐Jarisch effect but that the toxin further acts centrally to cause irregular breathholding and hypertension with tachycardia, leading ultimately to respiratory and circulatory failure.
EFFECTS OF KETAMINE ON VASCULAR SMOOTH MUSCLE FUNCTION
Authors: ALTURA B.M. , ALTURA B.T. , CARELLA ANTHONY 
Published: July 2012

In vitro studies were undertaken on rat aortic strips and portal vein segments to determine whether or not the amine‐type anaesthetic, ketamine, can exert direct actions on vascular smooth muscle.
Ketamine was found to inhibit development of spontaneous mechanical activity and lower basal tension. This action took place with ketamine concentrations found in anaesthetic plasma concentrations, i.e., 1 × 10−5 to 2 × 10−4 m.
Ketamine (10−5 to 10−3 m) dose‐dependently attenuated contractions induced by adrenaline, noradrenaline, angiotensin II, vasopressin and KCl. These inhibitory actions were Observed with ketamine added either before or after the induced contractions.
Ca2+‐induced contractions of K+‐depolarized aortae and portal veins were also attenuated, dose‐dependently, by ketamine.
In contrast to the above inhibitory actions, ketamine (2 × 10−6 to 1 × 10−4 m) was found to potentiate specifically 5‐hydroxytryptamine(5‐HT)‐induced contractions of both aortic and venous smooth muscle. However, this was only observed if ketamine was added after 5‐HT had initiated a contractile response.
All of the inhibitory, as well as 5‐HT‐potentiating, effects were completely, and almost immediately, reversed upon washing out the anaesthetic from the organ baths.
A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects induced by ketamine.
These data suggest that rat plasma concentrations of ketamine commonly associated with induction of surgical anaesthesia can induce, directly, relaxation and contractile potentiation of vascular muscle.
These diverse findings may aid in explaining the well‐known biphasic pressor actions of ketamine.
THE ACTIVITY OF SODIUM CROMOGLYCATE ANALOGUES IN HUMAN LUNG in vitro: A COMPARISON WITH RAT PASSIVE CUTANEOUS ANAPHYLAXIS AND CLINICAL EFFICACY
Authors: CHURCH MARTIN K. , GRADIDGE CAROLYN F. 
Published: July 2012

Eleven analogues of sodium cromoglycate have been tested for their ability to suppress histamine release induced by anti‐IgE from passively sensitized human lung fragments in vitro.
With the exception of WY 16922, which released histamine at high concentrations, all inhibited histamine release in a linear dose‐related manner.
The analogues were 30 to 1500 times more potent than sodium cromoglycate. However, their regression slopes of activity upon log‐concentration were only one‐third as steep as that for sodium cromoglycate, indicating a possible difference in their mechanism of action.
In comparison with sodium cromoglycate, the analogues were more potent in human lung than in rat passive cutaneous anaphylaxis (PCA); there was no quantitative correlation between potencies in the two tests.
The human lung model is not predictive of anti‐asthmatic activity in man as the six analogues tested clinically are less effective than sodium cromoglycate.
These results throw doubt on the use of models of mast cell degranulation in the search for Antiallergic drugs and, possibly, on the relative importance of mast cell degranulation in the pathogenesis of asthma.
SOME STUDIES ON THE RELEASE OF HISTAMINE FROM MAST CELLS STIMULATED WITH POLYLYSINE
Authors: ENNIS MADELEINE , PEARCE FREDERICK L. , WESTON PETER M. 
Published: July 2012

Polylysine is an extremely potent releaser of histamine from rat peritoneal mast cells. Isolated mesenteric mast cells of the rat also respond to the secretagogue but guinea‐pig mesenteric cells are unreactive.
The release does not require the presence of extracellular calcium ions but shows some dependence on internal stores of the cation.
The effect of polylysine is blocked by extremes of temperature and by metabolic inhibitors.
The release is very rapid and is virtually complete within 10 s of adding the inducer.
The release is unaffected by the Antiallergic drug, doxantrazole, but is inhibited by theophylline and disodium cromoglycate. The latter compounds are effective in both the presence and absence of added calcium. This result is discussed in terms of the postulated effect of the drugs on calcium transport.
ACEBUTOLOL, METOPROLOL AND PROPRANOLOL IN CONSCIOUS DOGS WITH CHRONIC HEART‐BLOCK: CHRONOTROPIC EFFECTS AND RELATION BETWEEN DEPRESSION OF VENTRICULAR ACTIVITY AND β‐ADRENOCEPTOR BLOCKING POTENCY
Authors: BOUCHER M. , DUCHENE‐MARULLAZ P. 
Published: July 2012

Atrial and ventricular chronotropic effects of acebutolol, metoprolol and propranolol were studied in conscious dogs with chronic heart‐block. Ventricular β‐adrenoceptor blocking activity was assessed for the three drugs against isoprenaline (1 μg/kg) under the same experimental conditions.
Acebutolol and metoprolol significantly increased atrial rate. The effect was proportional to the dose for acebutolol, independent for metoprolol. Propranolol had no significant effect on atrial rate. All three drugs significantly lowered ventricular rate in proportion to the dose.
Ventricular β‐blocking potencies of metoprolol and acebutolol were respectively 2 and 3 times weaker than that of propranolol as indicated by ED50 values.
The ventricular depressor effect observed was proportional to the degree of ventricular β‐blockade present, although this may not be the only factor involved.
COMPARATIVE ELECTROPHYSIOLOGICAL EFFECTS OF Org 6001, A NEW ORALLY ACTIVE ANTIDYSRHYTHMIC AGENT, AND LIGNOCAINE ON HUMAN VENTRICULAR MUSCLE
Authors: KANE KATHLEEN A. 
Published: July 2012

The electrophysiological effects of Org 6001, a new orally active antidysrhythmic agent, have been compared with those of lignocaine on the human ventricular action potential in vitro.
Org 6001 (4 to 16 mg/l) greatly reduced the maximum rate of depolarization (MRD) of the human ventricular action potential but had no effect on resting membrane potential or action potential amplitude.
The action potential duration at the 50% repolarization level, but not at the 90% repolarization level, was significantly reduced by Org 6001. The absolute refractory period was unchanged.
Lignocaine, at a concentration (4 mg/l) within the therapeutic range, had no significant effect on any measured parameter, either in muscle exposed to a normal (4.0 mm) or high (5.4 mm) extracellular potassium concentration ([K+]0).
Higher concentrations of lignocaine (8 to 16 mg/l) did, however, reduce MRD at both [K+]0 without changing resting membrane potential or action potential amplitude. The action potential duration was decreased slightly by these higher concentrations of lignocaine whilst the absolute refractory period was lengthened.
Org 6001 was found to be more potent than lignocaine in reducing MRD but, unlike lignocaine, the absolute refractory period was not prolonged. These compounds, therefore, differed in their electrophysiological effects on human ventricular muscle although both are characterized as being class 1 antidysrhythmic drugs.