bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE KINETICS OF COMPETITIVE ANTAGONISTS ON GUINEA‐PIG ILEUM
Authors: ROBERTS FIONA , STEPHENSON R.P. 
Published: July 2012

The kinetics of action of some competitive muscarinic and histamine antagonists were examined on guinea‐pig isolated ileum and their behaviour compared with the predictions of the interaction‐limited model described by Paton (1961).
The kinetics of antagonism were not consistent with the predictions of this model: (1) The apparent dissociation rate constant calculated from the decrease in occupancy on washout was not independent of the concentration of antagonist. (2) The dissociation rate constant of a ‘slow’ antagonist calculated from the change in occupancy when a ‘fast” antagonist was superimposed varied with the concentration of fast antagonist. (3) If the concentration of slow antagonist was increased when the fast antagonist was superimposed so that the equilibrium occupancy of the ‘slow” was the same as before, a transitional phase was observed.
The kinetics of antagonism were observed in longitudinal muscle strips and intact pieces of ileum, bathed in Tyrode or Krebs solution, and with isometric and isotonic recording. No evidence was found that the discrepancies between the interaction‐limited model and the observed kinetics could be accounted for by the experimental method used.
It is therefore concluded that either access is rate‐limiting in these circumstances or, if interaction is rate‐limiting, some alternative interaction‐limited model is required to describe the kinetics of antagonism. In either case it would seem unwise at this time to calculate antagonist‐receptor rate constants from the observed kinetics of antagonism.
THE CAT LUNG STRIP AS AN in vitro PREPARATION OF PERIPHERAL AIRWAYS: A COMPARISON OF β‐ADRENOCEPTOR AGONISTS, AUTACOIDS AND ANAPHYLACTIC CHALLENGE ON THE LUNG STRIP AND TRACHEA
Authors: LULICH K.M. , MITCHELL H.W. , SPARROW M.P. 
Published: July 2012

A new in vitro preparation, the isolated lung strip of the cat, is described for investigating the direct effect of drugs on the smooth muscle of the peripheral airways of the lung. The preparation comprises a thin strip of lung parenchyma which can be mounted in a conventional organ bath for isometric tension recording. Its pharmacological responses have been characterized and compared with the isolated tracheal preparation of the cat.
The lung strip exhibited an intrinsic tone which was relaxed by catecholamines, aminophylline and flufenamate. It was contracted strongly by histamine, prostaglandin F2α, acetylcholine, compound 48/80, potassium depolarizing solution and alternating current field stimulation. In contrast, the cat trachea was unresponsive to histamine and prostaglandin F2α and did not exhibit an intrinsic tone.
(–)‐Isoprenaline and (–)‐adrenaline were much more potent in relaxing the lung strip than the trachea. The potency order of relaxation responses to isoprenaline, adrenaline and (±)‐noradrenaline in the lung strip was isoprenaline > adrenaline > noradrenaline but in the trachea was isoprenaline > noradrenaline > adrenaline.
β2‐Adrenoceptor selective agonists salbutamol and terbutaline were more potent in the lung strip than the trachea, suggesting β2‐adrenoceptors predominated in the lung strip. Propranolol was equipotent in inhibiting isoprenaline relexations of the lung strip and trachea, whereas practolol was much less effective in inhibiting lung strip than trachea, further supporting a predominance of β2‐adrenoceptors in lung strip and β‐adrenoceptors in trachea.
Strong Schultz‐Dale type contractions were elicited in both lung strips and trachea by Ascaris lumbricoides antigen in actively sensitized cats. The initial phase of the contractile response of the lung strip following challenge was shown to be due to histamine release and was absent in the trachea. The delayed phase of the contraction which took several minutes to develop in both the mepyramine‐treated lung strip and trachea was not due to prostaglandins E1, F2α or bradykinin, the probable mediator being slow reacting substance of anaphylaxis (SRS‐A).
It is concluded that the isolated lung strip of the cat is useful as an in vitro model for investigating the effect of drugs on the smooth muscle of the peripheral airways of the lungs.
THE ACTIONS OF NATURAL SECRETIN ON THE SMALL INTESTINAL VASCULATURE OF THE ANAESTHETIZED CAT
Authors: RICHARDSON P.D.I. 
Published: July 2012

A plethysmographic preparation of cat jejunum was used to measure changes in tissue volume and capillary filtration coefficient (CFC), simultaneously with measurements of arterial and venous pressures, and total blood flow.
Secretin was infused and injected intravenously and also infused intra‐arterially in relatively small doses. Probable resulting blood concentrations were compared with those determined under physiological conditions in other investigations.
By intravenous or intra‐arterial infusion, secretin caused increases in CFC, indicating an increased functional exchange vessel area, and increases in jejunal volume, indicating increased vascular capacitance. The jejunal blood flow increased whilst the blood pressure remained essentially unchanged.
By intravenous injection, secretin caused rises in jejunal volume and reductions in calculated jejunal vascular resistance over the same dose range. Effects were statistically significant at 500 mu/kg and higher doses caused reductions in systemic arterial pressure.
The calculated peak blood concentrations of secretin resulting from the lower doses used in this investigation were of the same order of magnitude as those determined under physiological conditions in man.
It is possible that at physiological concentrations secretin causes an increased functional exchange vessel area in the small intestine, and may also increase the total blood flow through this tissue.
LABELLED DECAMETHONIUM IN CAT MUSCLE
Authors: CREESE R. , MACLAGAN JENNIFER 
Published: July 2012

Tritium‐labelled decamethonium was infused intravenously in 12 cats at final rates of 1.3–4.2 nmol kg−1 min−1 to produce a steady plasma concentration which ranged between 0.21‐1.3 μmol/1 in different experiments. Muscle contractions were elicited by nerve stimulation and the potential at the end‐plate regions of superficial fibres was recorded by extracellular electrodes.
Under these conditions, it was not possible to obtain a steady degree of neuromuscular block. The initial decrease in muscle contractions was followed by recovery towards the original value although the concentration of decamethonium in the plasma remained constant, or in some cases rose. The initial depolarization of the end‐plate region also waned during the constant infusion of the drug.
Once the twitch tension had returned to control values during infusion of the drug, prolongation of the infusion for a total of four hours did not produce a secondary neuromuscular block.
Scintillation counting showed that during infusion of labelled decamethonium the radioactivity of the muscles increased progressively with time. The uptake was less in the soleus muscle than in the fast‐contracting flexor longus digitorum and extensor longus digitorum muscles. Muscles which had been denervated 12–13 days previously showed a greater uptake of labelled drug than control muscles from the contralateral limb.
The labelled drug was localized by autoradiography of frozen sections of leg muscles following intra‐arterial injection of decamethonium. Grain counts in individual fibres showed that small amounts of decamethonium had entered the muscle fibres along their entire length, and there was increased uptake of the drug into the cell in the region of the end‐plate.
The mechanisms underlying the waning of the pharmacological response during constant application of depolarizing drugs are discussed.
INHIBITORY INNERVATION OF CAT SPHINCTER OF ODDI
Authors: PERSSON C.G.A. 
Published: July 2012

Electrical stimulation with trains of 0.1‐0.2 ms pulses of the cat isolated sphincter of Oddi inhibited the spontaneous contractile activity and lowered base‐line tension considerably. A contraction usually followed the period of stimulation.
These inhibitory effects were prevented by tetrodotoxin 0.1‐0.5 μg/ml but were not reduced by hexamethonium, morphine, or blockade of α‐ or β‐adrenoceptors or cholinoceptors with phenoxybenzamine propranolol or atropine, respectively.
Adenosine‐5′‐triphosphate (ATP) and adenosine‐5′‐diphosphate (ADP) inhibited the spontaneous sphincter activity and caused relaxation thus mimicking the effects of the C‐terminal octapeptide of cholecystokinin (C8‐CCK), isoprenaline and prostaglandins E1 and E2.
ATP alone (> 100 μg/ml) or ATP (> 10 μg/ml) plus dipyridamole (1 μg/ml), relaxed the sphincter to the same degree as did the field stimulation.
In sphincters maximally contracted by acetylcholine, the effect of stimulation was more marked than that recorded in uncontracted preparations.
The present findings suggest that the sphincter of Oddi receives inhibitory nerves that are neither cholinergic nor adrenergic.
EFFECT OF MORPHINE AND NALOXONE ON PRIMING‐INDUCED AUDIOGENIC SEIZURES IN BALB/c MICE
Authors: CHEN C.S. , GATES G.R. , REYNOLDSON J.A. 
Published: July 2012

Morphine (1–200 mg/kg, s.c.) reduced the incidence and prolonged the latency of priming‐induced audiogenic seizures in a dose‐dependent manner.
This effect was reversed by naloxone (1 and 2 mg/kg) although naloxone was itself inactive.
This priming‐induced seizure model may be useful in the study of tolerance and physical dependence.
ON THE FUNCTIONAL COUPLING OF NEUROTRANSMITTER UPTAKE AND RELEASE IN BRAIN
Authors: COTMAN C.W. , HAYCOCK J.W. , LEVY W.B. 
Published: July 2012

Isolated synaptosomal fractions from mouse forebrains were incubated with [14C]‐γ‐aminobutyric acid ([14C]‐GABA). Release of the accumulated label in high potassium solution was measured.
The fractional release dependent upon calcium was decreased by raising the concentration of [14C]‐GABA during labelling but was not affected by altering the time allowed for labelling or the time between labelling and stimulation.
These data suggest that extracellular GABA gains rapid access to available intraterminal pools. The relative distribution of the accumulated GABA in different pools can be influenced by the concentration of GABA in the incubation medium but, once ‘stored’, there is no net redistribution of accumulated GABA in the absence of stimulation.
THE EFFECT OF DIBUTYRYL CYCLIC ADENOSINE‐3′,5′‐MONOPHOSPHATE ON PROTEIN SECRETION FROM THE RAT EXOCRINE PANCREAS in vitro
Authors: FAST D. , TENENHOUSE A. 
Published: July 2012

The mechanism by which dibutyryl cyclic adenosine‐3′‐5′‐monophosphate (dibutyryl cyclic AMP) potentiates the secretory effect of carbachol in rat exocrine pancreas was investigated.
Dibutyryl cyclic AMP potentiated the secretory effect of carbachol only at carbachol concentrations ⋝10−7 mol/l; was independent of carbachol at concentrations > 10−7 mol/l and was inversely proportional to extracellular [Ca2+].
Carbachol increased and dibutyryl cyclic AMP reduced the rate of 45Ca efflux from the tissue.
A‐23187 stimulated 3H‐protein release in the presence of Ca2+ and this effect was potentiated by dibutyryl cyclic AMP; the degree of potentiation was inversely proportional to extracellular [Ca2+]. At 10−3 mol/l [Ca2+] the potentiation occurred only at ionophore concentrations ⋜ 10−6 mol/litre.
These results support the hypothesis that dibutyryl cyclic AMP potentiates the effect of secretagogues in rat exocrine pancreas by maintaining an elevated intracellular calcium concentraion. It does so by inhibiting Ca2+ efflux. The results also suggest that the limiting factor in carbachol‐stimulated secretion, at all concentrations of carbachol, is intracellular [Ca2+].
TOLERANCE PATTERN OF THE ANOREXIGENIC ACTION OF AMPHETAMINES, FENFLURAMINE, PHENMETRAZINE AND DIETHYLPROPION IN RATS
Authors: GHOSH M.N. , PARVATHY S. 
Published: July 2012

The tolerance pattern to anorectic drugs was studied in starved rats by measuring two consecutive 2 h food intakes.
There was a reduction in the first 2 h food intake with development of complete tolerance after fenfluramine and phenmetrazine, and of partial tolerance after amphetamine, (+)‐amphetamine and diethylpropion.
During the second 2 h intake, the anorectic effect was transient after fenfluramine and diethylpropion; while there was an absolute increase in the intake after amphetamine and (+)‐amphetamine.
A pair‐feeding experiment revealed that the increase in the second 2 h food intake was not a direct effect of the drug but a consequence of the deficit in food intake during the preceding 2 hours.
There was an overall correlation between the food and water intake.
A significant loss in body weight was observed after amphetamine, fenfluramine and phenmetrazine but not after (+)‐amphetamine or diethylpropion.
The results indicate that so‐called tolerance to the anorexigenic effect of drugs is apparent rather than real and that the duration of food access is a determining factor. The body weight changes may be brought about by the metabolic effects of these drugs rather than their effect on food and water intake.
DUAL EFFECTS OF ASPIRIN IN GUINEA‐PIG LUNGS
Authors: MIELENS Z. E. , ROSENBERG F. J. 
Published: July 2012

Dual effects of aspirin were demonstrated in guinea‐pig lungs: (a) aspirin (3.3 mg/kg i.v.) antagonized bronchoconstriction induced by slow reacting substance of anaphylaxis (SRS‐A); (b) aspirin produced bronchoconstriction when injected in the presence of propranolol into guinea‐pigs in vivo at 330 mg/kg, or into guinea‐pig isolated lungs in vitro as a 4% solution (40 mg/ml).
The severity of bronchoconstriction following administration of aspirin was directly related to the degree of β‐adrenoceptor blockade and to the age of the guinea‐pigs. Aspirin‐induced bronchoconstriction was prevented in vivo and in vitro by atropine and it could be reversed in vivo by atropine. Aspirin‐induced bronchoconstriction was not inhibited by vagotomy or phenoxybenzamine.
These data suggest that the mechanism involved in aspirin‐induced bronchoconstriction may be local cholinergic stimulation and that reduced β‐adrenergic drive may be a predisposing factor.
OBSERVATIONS ON THE PHARMACOLOGY OF CHOLINOCEPTIVE NEURONES IN THE RAT BRAIN STEM
Authors: BRADLEY P.B. , DRAY A. 
Published: July 2012

The pharmacology of spontaneously active cholinoceptive neurones in the brain stem of rats anaesthetized with urethane has been investigated using microiontophoresis to administer muscarinic and nicotinic agonists and antagonists.
Acetylcholine (ACh) excited most cells but occasionally depressed their activity. Muscarine, and the muscarinic agonists methacholine and bethanechol produced prolonged excitation or inhibition of cells whereas nicotine produced prolonged excitations but no inhibitions.
Atropine selectively antagonized ACh excitations and both excitation and inhibition of neuronal activity produced by muscarine and muscarinic agonists, but not the excitations produced by nicotine, glutamate or dl‐homocysteic acid.
Dihydro‐β‐erythroidine (DHBE) and tubocurarine antagonized both ACh and nicotine excitations but not those induced by glutamate or dl‐homocysteic acid. Inhibitions by ACh or muscarine were not affected.
It is concluded that excitations of cholinoceptive neurones in the rat brain stem may be mediated by activation of both muscarinic and nicotinic receptors whereas inhibitions are mediated by activation of a muscarinic receptor.
EFFECTS OF CONTRACEPTIVE AGENTS ON DRUG METABOLISM IN VARIOUS ANIMAL SPECIES
Authors: BRIATICO G. , GUISO G. , JORI A. , RAVAZZANI C. 
Published: July 2012

The effect on liver microsomal enzyme activity of three steroid contraceptive drug (SCD) combinations was compared in rats, mice and guinea‐pigs. Lynestrenol plus mestranol, norethisterone plus mestranol and norethynodrel plus mestranol were given orally for 4 consecutive days (acute treatment) or 30 days (chronic treatment) at various doses eliciting an experimentally controlled antifertility activity which varied in its extent.
In rats and mice all the combined treatments (with the exception of norethynodrel plus mestranol in mice) were active as inducers of liver microsomal enzymes. This induction seems to be mediated mainly by the progestogenic compounds. Oestrogens showed a very poor effect bordering on significance only in a few cases.
No effect on liver microsomal protein or cytochrome P 450 concentration was obtained after treatment with doses capable of increasing the microsomal enzyme activity.
The activity of the liver microsomal enzymes did not appear to be reduced immediately (2 h) after the last administration of the SCD given during 4 or 30 days.
Contraceptive treatments at doses capable of eliciting complete antifertility activity were inactive on liver microsomal enzyme activity in guinea‐pigs.
STIMULATION OF PROSTAGLANDIN BIOSYNTHESIS BY DRUGS: EFFECTS in vitro OF SOME DRUGS AFFECTING GUT FUNCTION
Authors: COLLIER H.O.J. , McDONALD‐GIBSON WENDY J. , SAEED S.A. 
Published: July 2012

Low concentrations of several emetic, purgative or irritant drugs in the absence of added co‐factors stimulated conversion of arachidonic acid to prostaglandin E2 and F2α by prostaglandin synthetase extracted from bull seminal vesicles (BSV prostaglandin synthetase). Their effect was dependent on concentration and time.
Stimulation of BSV prostaglandin synthetase by apomorphine, aloes, tyramine or zingerone was increased several‐fold by addition of reduced glutathione to the incubation medium, whereas hydroquinone, a phenolic co‐factor of prostaglandin synthetase caused slight depression.
From this finding and from the observation that many of the stimulant drugs possess a phenolic group, whereas their inactive relatives lack such a group, it is suggested that these stimulant drugs act as co‐factors for prostaglandin synthetase in place of hydroquinone.
Aloes, tyramine, ethanol and quipazine also produced a dose‐related increase in resting tone of the isolated fundus of the rat stomach. This increase occurred at concentrations comparable to those effective in stimulating BSV prostaglandin synthetase, and was abolished by acetylsalicylate.
These findings support the view that certain drugs exert some of their pharmacological effects by stimulating prostaglandin synthetase.
BRADYKININ AND FUNCTIONAL VASODILATATION IN THE SALIVARY GLAND
Authors: FERREIRA S.H. , SMAJE L.H. 
Published: July 2012

Blood flow through the submandibular gland of the dog was measured and the venous effluent monitored for potential mediators of the functional vasodilatation by passing it over a series of assay tissues.
On chorda lingual nerve stimulation there was salivation, an increased blood flow and the release of a bradykinin‐like substance (kinin) into the venous effluent.
In about half of the preparations, increasing the frequency of stimulation from 2 to 10 Hz led to an increased output of kinin, whereas in the others successive stimulations led to a decreasing output of kinin in the face of normal secretory and vascular responses.
Following the administration of atropine, the vasodilatation persisted, salivation was abolished and after several stimulations kinin release could no longer be detected.
Release of prostaglandin did not appear to be responsible for the vasodilatation.
It is concluded that neither kallikrein nor kinin is the main mediator of parasympathetic vasodilatation in the salivary gland.
THE DENERVATED CREMASTER MUSCLE OF THE GUINEA‐PIG AS A PHARMACOLOGICAL PREPARATION
Authors: DALE M. MAUREEN , EVINÇ AKGÜN , VINE PAULINE 
Published: July 2012

The pharmacological responses of both denervated and innervated cremaster muscle preparations from the guinea‐pig have been investigated and compared. Acetylcholine (ACh) dose‐response curves were obtained in both preparations. The affinity constants for (+)‐tubocurarine and for atropine were calculated and indicated that the ACh receptors in both preparations were nicotinic.
Histamine dose‐response curves could be obtained only in the denervated preparation. The response was unaltered by metiamide, and the affinity constant for mepyramine fitted in with those previously obtained by others on ileum and trachea, indicating that the histamine receptors are H1 in type.
Sustained contractions were obtained to adrenaline and noradrenaline but not isoprenaline, with the denervated preparations.
Schultz‐Dale responses were obtained with denervated muscle in sensitized guinea‐pigs. This preparation did not respond to 5‐hydroxytryptamine, bradykinin, or the slow‐reacting substance of anaphylaxis.
EFFECTS OF KETAMINE ON THE PERIPHERAL AUTONOMIC NERVOUS SYSTEM OF THE RAT
Authors: CLANACHAN A.S. , McGRATH J.C. 
Published: July 2012

The effects of ketamine (2‐(o‐chlorophenyl) 2‐methylaminocyclohexanone) (2–50 mg/kg) on the responses of the pithed rat arterial pressure, anococcygeus muscle and colon to selective stimulation of the spinal autonomic outflows were examined.
Ketamine depressed the vasopressor response produced by stimulation of the lumbar sympathetic outflow in a dose‐dependent manner but did not significantly affect the pressor response to intravenous noradrenaline (NA) administration.
Ketamine depressed the motor responses of the anococcygeus to stimulation of the pre‐ganglionic lumbar sympathetic outflow or to stimulation of post‐ganglionic fibres in the sacral region in a dose‐dependent manner, the response to preganglionic stimulation being relatively more sensitive to such depression. The anococcygeus response to NA was significantly potentiated with doses of ketamine of 20 mg/kg and 50 mg/kg.
Ketamine depressed the motor response of the smooth muscle of the colon to stimulation of the sacral parasympathetic outflow in a dose‐dependent manner and at lower doses than were required to produce an equivalent depression of the sympathetic responses in the other tissues.
A comparison was made of the effects of ketamine and cocaine on the motor responses of the anococcygeus muscle in vitro to NA, carbachol and field stimulation. Both ketamine and cocaine produced a non‐specific depression of all responses at high doses whereas cocaine but not ketamine produced a large potentiation of NA and motor nerve responses at lower doses.
The results are discussed in relation to the hypothesis that ketamine might elevate blood pressure in conscious animals and man by potentiating vascular adrenergic responses.
RENAL FUNCTION AND RENAL VENOUS PROSTAGLANDIN CONCENTRATIONS DURING DIFFERENT STAGES OF EXPERIMENTAL RENAL HYPERTENSION IN THE RAT
Authors: SMITH G.W. , SOMOVA LILIANA I. 
Published: July 2012

Renal hypertension was produced in rats and the changes in renal function, renal venous prostaglandin E2 and F2α concentrations and secretion rates were studied at various times.
Renal plasma flow transiently fell in the ischaemic kidney 2 weeks after clamping, whilst that of the other kidney did not change. Glomerular filtration rate remained constant in both kidneys throughout the entire study.
Prostaglandins E2 and F2α concentrations rose in the venous plasma from the ischaemic kidney, but did not change in the other kidney and appeared to be inversely related to renal plasma flow.
Calculated secretion rate of both prostaglandins fell in the ischaemic kidney and did not change in the other kidney.
Clamping the second kidney, two weeks after the first, caused a further elevation in blood pressure, a fall in renal plasma flow and a fall in prostaglandin secretion rate in both kidneys.
The implications of these prostaglandin changes are discussed.