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Biomedical subjects

M E Parsons

Publications and source records attributed to M E Parsons.

At least 73 records · Page 4Linked to original sources
PubMed1981

The effect of cimetidine on basal and stimulated pepsin secretion in the isolated whole stomach of the rat.

1 The isolated stomach preparation of the immature rat has been used to study the stimulation and inhibition of pepsin secretion. 2 The isolated stomach secretes a basal level of pepsin. High concentrations (10(-3)M) of the H2-receptor antagonist, cimetidine, and the muscarinic receptor blocking drug, atropine, did not affect this secretion in a manner which was consistently of statistical significance. 3 Concentrations of histamine of 10(-5)M, 10(-4)M and 10(-3) M stimulated maximum levels of pepsin output of 126%, 155% and 299% respectively of control. There was no evidence that this secretion was secondary to the stimulation of acid secretion. 4 Cimetidine (10(-4)M and 10(-3)M) produced a dose-related inhibition of the pepsin output to 10(-3)M histamine, suggesting that histamine H2-receptors mediate this response. 5 Atropine (10(-3)M) had no effect on the pepsin response to 10(-3)M histamine, suggesting that muscarinic mechanisms play no part, even modulatory, in this secretion.

Animals↗
PubMed1980

Ethanol-stimulated acid secretion in the isolated whole stomach of the rat.

The application of ethanol to the serosal surface of the isolated whole rat stomach stimulated a high rate of acid secretion, with a maximum response being obtained to 4% v/v ethanol. This acid response to ethanol was not inhibited by high concentrations (1 mM) of atropine or cimetidine, indicating that the response was probably not mediated by either histamine, gastrin or acetylcholine. These results using the secretory antagonists were confirmed by experiments in an isolated gastric mucosa preparation. The acid response to ethanol was significantly, but not completely inhibited by 10 mM thiocyanate, indicating the existence of an acid component of non-arietal cell origin in the mucosal bathing solution. However, analysis of the mucosal solution failed to reveal the presence of an acidic metabolite of ethanol.

Animals↗
PubMed1979

The effect cystamine on gastric secretion in the rat.

The effects of cystamine on gastric secretion were studied in conscious and anaesthetized rat preparations. In the conscious gastric fistula rat cystamine inhibited the basal acid output but increased pepsin output. This pepsinogogue action was inhibited by both atropine and metiamide. In the anaesthetized rat cystamine stimulated gastric acid output, an effect blocked by cimetidine which had an inhibitory E.D. 50 which was not significantly different from that obtained against histamine-stimulated secretion in this preparation. Atropine at high doses failed to inhibit the response. Depletion of mast cell histamine by compound 48/80 the secretory response to cystamine. In the light of these results possible mechanisms of action for the secretagogue effects of cystamine are discussed.

Anesthesia↗
PubMed1979

Inhibition of pepsin secretion by metiamide and atropine in the conscious rat.

The inhibition of pepsin secretion by metiamide and atropine has been studied in the gastric fistula rat and the Heidenhain pouch rat. A comparison of the effectiveness of metiamide and atropine in inhibiting pepsin secretion was made by using doses of the antagonists which produced a similar level of inhibition of acid secretion. In the gastric fistula rat both atropine and metiamide inhibited the basal pepsin output, but atropine was more effective than metiamide in this respect. In the Heidenhain pouch rat a large dose of metiamide which inhibited bethanechol-stimulated acid secretion had no significant effect on the corresponding output of pepsin. In this preparation atropine inhibited both acid and pepsin secretion. Possible reasons for the differences in the two preparations are discussed.

Animals↗
PubMed1979

Investigation of the role of extracellular calcium in the control of acid secretion in the isolated whole stomach of the rat.

1 An isolated stomach preparation from immature rats has been used to study the role of extracellular calcium in the control of gastric acid secretion. Calcium was removed from both the serosal and mucosal solutions either in the absence of a chelating agent or in the presence of EGTA.2 Removal of calcium in the absence of EGTA had no significant effect on basal acid secretion or the acid responses to gastrin and dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP). Under the same conditions there was a marked potentiation of the acid response to histamine, and a reduction of the acid response to acetylcholine which was readily reversed on restoring calcium to the bathing solutions.3 Removal of calcium in the presence of EGTA caused an inhibition of basal acid secretion and of the acid responses to histamine and db cyclic AMP. In each case this reduction in acid output was readily reversed on bathing the stomachs in normal calcium-containing (2.5 mM Ca(2+)) EGTA-free solutions.4 The inhibition of the acid response to histamine produced by Ca(2+)-free solutions which contained EGTA was not reversed on bathing the stomachs in solutions that contained both EGTA (0.1 mM) and an excess of calcium (2.5 mM).5 The removal of extracellular calcium in the absence of EGTA provided evidence that the secretion of H(+) ions is dependent under some conditions on calcium ions. The possibility cannot be excluded that EGTA itself exerts an inhibitory influence on the process of acid secretion.

Acetylcholine↗
PubMed1979

Reduction by cimetidine of acute gastric hemorrhage caused by reinfusion of blood after exposure to exogenous acid during gastric ischemia in rats.

The present study has been made in anesthetized rats to characterize conditions of exposure to acid and extent of ischemia which determine the development of gastric hemorrhage. Gastric hemorrhage occurred in rats subjected to shock during exposure of the gastric lumen to acid after the reinfusion of withdrawn blood. When the acid concentration was constant, bleeding was dependent on the degree of shock. When hemorrhage shock was constant, bleeding from the stomach appeared pH dependent, although this did not quite achieve statistical significance. Cimetidine 2 x 10(-6) mol kg-1 min-1 (30 mg kg-1 hr-1) and 1 x 10(-5) mol kg-1 min-1 (150 mg kg-1 hr-1) significantly reduced gastric hemorrhage whether given prophylactically before gastric injury or therapeutically after completion of gastric injury. Because protection can be demonstrated against an injury involving exogenous acid and after the injury has been established, it is probable that the effectiveness of cimetidine in these studies is independent of its antisecretory effects.

Acute Disease↗
PubMed1978

Inhibition by metiamide of secretagogue-induced gastric acid secretion in the conscious Heidenhain pouch rat.

1. The inhibition by metiamide of gastric of gastric acid secretion in response to histamine, pentagastrin and bethanechol has been investigated in the conscious Heidenhain pouch rat. 2. Histamine alone stimulated only a low rate of acid secretion. This response was markedly potentiated in the presence of mepyramine. 3. Metiamide at a dose of 0.15 mumole . kg-1 . min-1 I.V. significantly inhibited the acid secretory responses to histamine (in the presence of mepyramine) and pentagastrin. In each case the inhibition of acid output was the result of a significant decrease in both secretory volume and acid concentration. 4. Metiamide at a dose of 0.15 mumole . kg-1 . min-1 I.V. did not inhibit bethanechol-stimulated acid secretion. Increasing the dose of metiamide to 1.0 mumole . kg 1 . min-1 I.V. did produce a significant inhibition. In contrast with histamine and pentagastrin, metiamide inhibited bethanechol-stimulated secretion only by reducing acid concentration; there was no significant decrease in the gastric secretory volume. 5. It is concluded that these results are consistent with the view that histamine and pentagastrin share a common pathway in stimulating gastric acid secretion in the rat. The role of histamine in the control of bethanechol-stimulated acid secretion remains unclear.

Animals↗
PubMed1978

Characterization and development of cimetidine as a histamine H2-receptor antagonist.

The concept of two classes of histamine receptor, H1 and H2, is introduced and the chemical derivation of histamine H2-receptor antagonists is outlined briefly. Starting from the structure of histamine, chemical modification led eventually to burimamide, the first described histamine H2-receptor antagonist. Further stepwise modifications ultimately afforded metiamide and cimetidine. In vitro studies show that cimetidine is a specific competitive histamine H2-receptor antagonist. In vivo, it is a potent inhibitor of histamine-stimulated gastric acid secretion in rats and dogs after both intravenous and oral administration. It is equally potent as an inhibitor of pentagastrin-stimulated secretion. The evidence suggests that cimetidine inhibits gastric acid secretion through blockade of histamine H2-receptors in the gastric mucosa. Cimetidine has been shown to have low acute toxicity. Repeated dose studies of up to 24 months in rats and up to 12 months in dogs have been carried out and the results are presented and discussed. There is no known toxic effect which would limit the usefulness of cimetidine in man.

Androgen Antagonists↗