Action of histamine and vasoactive intestinal peptide (VIP), on cyclic AMP in gastric glands isolated from human fetal stomach

Summary Histamine and VIP produce an elevation of cAMP production in gastric glands isolated from the human fetal stomach at 15 weeks of gestation. These effects were attributed to the activation of 2 distinct receptor-cAMP systems, one being sensitive to histamine in parietal cells, and the other being sensitive to VIP in muco-peptic cell populations. The results suggest that histamine and VIP may play a role in inducing gastric secretion during fetal life in man.     

VIP and histamine H2 receptor activity in human fetal gastric glands

Vasoactive intestinal peptide (VIP, EC50 = 6.4 X 10(-10)M) and histamine (EC50 = 3 X 10(-6)M) activated the cyclic AMP generating system in gastric glands isolated from two human fetuses at 23 weeks gestation. Histamine antagonism by the H2 receptor blockers cimetidine (Ki = 0.35 X 10(-6)M) and ranitidine (ki = 0.51 X 10(-7)M) clearly characterized the histaminic activation as being of the H2 type. It is suggested that these two vasoactive hormones may operate as neurocrine/paracrine regulators of the differentiation and/or function of the human gastric mucosa in utero.     

VIP and histamine H2 receptor activity in human fetal gastric glands

Summary Vasoactive intestinal peptide (VIP, EC₅₀=6.4×10^–10 M) and histamine (EC₅₀=3×10^–6 M) activated the cyclic AMP generating system in gastric glands isolated from two human fetuses at 23 weeks gestation. Histamine antagonism by the H₂ receptor blockers cimetidine (Ki=0.35×10^–6 M) and ranitidine (ki=0.51×10^–7 M) clearly characterized the histaminic activation as being of the H₂ type. It is suggested that these two vasoactive hormones may operate as neurocrine/paracrine regulators of the differentiation and/or function of the human gastric mucosa in utero.     

Gastrin: obligatory intermediate in the postprandial mobilization of gastric histamine in the rat.

In unoperated fasted rats, feeding raised the serum gastrin concentration, reduced the gastric mucosal histamine content and activated the gastric histidine decarboxylase. The reduction of gastric histamine and activation of histidine decarboxylase was induced also by the injection of pentagastrin. In antrectomized rats, feeding failed to produce these effects. Injection of pentagastrin, however, still lowered gastric histamine and activated gastric histidine decarboxylase. Thus, antral gastrin seems to be an obligatory mediator of the postprandial activation of histidine decarboxylase and mobilization of histamine.     

Effect of stimulation of vagus nerves on gastric tissue histamine concentration in albino rats.

2 different time schedules were applied in order to stimulate vagus nerves around the oesophagus at the region of the cardio-oesophageal junction. The result shows a significant reduction in gastric tissue histamine concentration following vagal stimulation, the reduction being more when the duration of stimulation was longer.     

Gastrin: Obligatory intermediate in the postprandial mobilization of gastric histamine in the rat

Summary In unoperated fasted rats, feeding raised the serum gastrin concentration, reduced the gastric mucosal histamine content and activated the gastric histidine decarboxylase. The reduction of gastric histamine and activation of histidine decarboxylase was induced also by the injection of pentagastrin. In antrectomized rats, feeding failed to produce these effects. Injection of pentagastrin, however, still lowered gastric histamine and activated gastric histidine decarboxylase. Thus, antral gastrin seems to be an obligatory mediator of the postprandial activation of histidine decarboxylase and mobilization of histamine.Acknowledgments. Grant support from the Swedish and Danish Medical Research Councils (14P-4822, 04X-1007, 17X-4144 and 512-2540).     

Effect of bilateral adrenalectomy and parenteral betamethasone on gastric mucosal mast cell population in albino rats

Summary The histamine-laden mast cells gastric mucosa in albino rats are shown to degranulate on administration of Betamethasone, but they increase in number in adrenalectomized rats. It is concluded that Betamethasone, and also adrenal glucocorticoids incrase gastric secretion by liberating histamine from mast cells and histamine in turn acts on the gastric glands.     

Effect of bilateral adrenalectomy and parenteral betamethasone on gastric mucosal mast cell population in albino rats.

The histamine-laden mast cells of gastric mucosa in albino rats are shown to degranulate on administration of Betamethasone, but they increase in number in adrenalectomized rats. It is concluded that Betamethasone, and also adrenal glucocorticoids increase gastric secretion by liberating histamine from mast cells and histamine in turn acts on the gastric glands.     

Effect of stimulation of vagus nerves on gastric tissue histamine concentration in albino rats

Summary 2 different time schedules were applied in order to stimulate vagus nerves around the oesophagus at the region of the cardio-oesophageal junction. The result shows a significant reduction in gastric tissue histamine concentration following vagal stimulation, the reduction being more when the duration of stimulation was longer.The authors are grateful to Dr V. Srinivasan, Director, Sarabhai Research Centre, Baroda, India, for donating the animals required for carrying out this work.     

Colchicine inhibits stimulated release of gastric histamine but not activation of histidine decarboxylase.

In the rat, gastric mucosal histamine is mobilized and histidine decarboxylase activated by treatment with insulin or pentagastrin. Colchicine pretreatment prevented the histamine release without preventing the enzyme activation. The results suggest a) that histamine release and histidine decarboxylase activation are independent events, and b) that microtubules are involved in the release of histamine.     

Colchicine inhibits stimulated release of gastric histamine but not activation of histidine decarboxylase

Summary In the rat, gastric mucosal histamine is mobilized and histidine decarboxylase activated by treatment with insulin or pentagastrin. Colchicine pretreatment prevented the histamine release without preventing the enzyme activation. The results suggest a) that histamine release and histidine decarboxylase activation are independent events, and b) that microtubules are involved in the release of histamine.     

Pentagastrine,histamine et acide ascorbique de la muqueuse gastrique chez le rat

Summary Pentagastrin and histamine, 2 potent gastric acid stimulants, lower ascorbic acid in the rat's gastric mucosa. They give the same result as nerve stimulation by desoxyglucose. Explanation of ascorbic acid function in gastric physiology needs further work.     

Effect of pylorus ligation on gastric mucosal mast cell population in normal and adrenalectomised albino rats

Summary Pylorus ligation in normal albino rats acts like a stressor leading to degranulation of mast cells in gastric mucosa, thereby decreasing their number. This decrease is less pronounced when pylorus ligation is done in adrenalectomized rats. This implies that action of a stressor on gastric function involves the adrenal steroids which liberate the powerful gastric stimulant histamine from gastric mucosal mast cells.     

Effect of pylorus ligation on gastric mucosal mast cell population in normal and adrenalectomised albino rats.

Pylorus ligation in normal albino rats acts like a stressor leading to degranulation of mast cells in gastric mucosa, thereby decreasing their number. This decrease is less pronounced when pylorus ligation is done in adrenalectomized rats. This implies that action of a stressor on gastric function involves the adrenal steroids which liberate the powerful gastric stimulant histamine from gastric mucosal mast cells.     

Gastric secretion during anaesthesia and its inhibition by metiamide and other drugs.

The histamine H2-receptor antagonist, metiamide, inhibits the acid gastric secretion produced by chloralose-urethane anaesthesia in dogs carrying gastric cannulae chronically. This secretion is also prevented by atropine and hexamethonium. "Spontaneous" gastric secretion of vagal origin in conscious dogs is also blocked by metiamide.     

Effect of daily parenteral injection of betamethasone on histamine concentration of gastric tissue in albino rats

Gastric tissue histamine concentration was determined in albino rats following daily parenteral injection of betamethasone over a period of 12 days. The result shows a highly significant fall in gastric tissue histamine concentration in comparison with that in saline-treated albino rats over a similar period.     

Effect of daily parenteral injection of betamethasone on histamine concentration of gastric tissue in albino rats

Summary Gastric tissue histamine concentration was determined in albino rats following daily parenteral injection of betamethasone over a period of 12 days. The result shows a highly significant fall in gastric tissue histamine concentration in comparison with that in saline-treated albino rats over a similar period.This investigation was carried out as a part of a project supported by a research grant from Medical Research Centre, Bombay Hospital Trust, Bombay, India.     

Stimulation of pyruvate carboxylation by gastric secretagogues

Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa.     

Modification of the action of pentagastrin on acid secretion by botulinum toxin.

I.v botulinum toxin after 60-90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin.     

Stimulation of H+ ion secretion from the isolated mouse stomach by sodium fluoride

Summary The effect of sodium fluoride on H⁺ ion secretion was investigated in the isolated distended mouse stomach. It was found that sodium fluoride on its own caused dose-related stimulation of H⁺ ion secretion. Sodium fluoride did not inhibit H⁺ ion secretion induced by histamine. The possible mechanisms involved are discussed. It is considered that sodium fluoride might stimulate H⁺ ion secretion by causing histamine release and by increasing cyclic AMP formation in the intact gastric mucosa.