Gastrin Produces an Immediate and Dose-Dependent Histamine Release Preceding Acid Secretion in the Totally Isolated, Vascularly Perfused Rat Stomach

Abstract

Increasing doses of gastrin 1-17 (G1-17) were administered to totally isolated, vascularly perfused rat stomachs prestimulated with the phosphodiesterase inhibitor isobutyl methylxanthine (IMX). Vascular and luminal histamine outputs and luminal acid output were monitored at short intervals. G1-17 induced an immediate histamine release to the vascular perfusate, preceding the increase in acid secretion by approximately 10 min. Vascular histamine output increased from a base line (IMX only) of 4.0 +/- 0.4 to a maximum of 34.5 +/- 7.3 nmol/60 min (mean +/- SEM) after 1040 pM G1-17, and acid output from 8.0 +/- 2.8 to 61.5 +/- 7.0 mumol/60 min after 520 pM G1-17. Acid output was correlated to vascular histamine release (r = 0.64, p less than 0.001). Gastrin produced a histamine release giving gastric venous concentrations of the same magnitude as the concentration of histamine necessary to induce a comparable acid response. Histamine release to the lumen, on the other hand, paralleled the acid secretion in time, suggesting it to be a passive phenomenon secondary to acid secretion. Thus, the present study for the first time shows that gastrin induces vascular histamine release of such a magnitude that this substance could be the mediator of the gastrin effect on acid secretion.

The effect of the peroxisome proliferator ciprofibrate on the gastric mucosa and particularly the gastrin cell

“…It should, however, be mentioned that gastrin has a negative tropic effect on the oxyntic D cell (Chen et al 1992) partly explaining the reduction in somatostatin mRNA abundance. The marked increase in HDC mRNA in the oxyntic mucosa simply reflects the well-known stimulatory effect of gastrin on the ECL cell (Sandvik et al 1987) and an increase in HDC mRNA abundance (Sandvik et al 1994).…”

Review article: the pharmacological inhibition of gastric acid secretion—tolerance and rebound

“…While a few older studies 8,9 suggested that histamine release could be part of the acid stimulatory process, unequivocal evidence for the immediate and potent effect of gastrin on histamine release was not obtained until 1987. 10 Today, it is clear that the enterochromaf®ne-like (ECL) cell synthesizes histamine in a wide range of species, 11 and that this cell is the only histamine-synthesizing cell with gastrin receptors. 12±14 Moreover, in all species where it has been possible to carry out satisfactory studies, it has been shown that gastrin stimulates the release of gastric mucosal histamine.…”

Molecular control of peptide hormone and receptor expression

“…An alternative theory, the 'transmission' hypothesis (Code, 1977;Black & Shankley, 1987), is that acetylcholine and gastrin act by releasing histamine, which then serves as the final common stimulant of the parietal cell. Support for this idea comes from pharmacological analyses of H-2 receptor antagonist actions in vivo (Black & Shankley, 1987) and from the finding that gastrin and muscarinic agonists release histamine from the totally isolated, vascularly perfused rat stomach, and increase activity of histidine decarboxylase (EC 4.1.1.22; HDC), the enzyme that converts histidine to histamine in the enterochromaffin-like (ECL) cell of the gastric corpus mucosa (Hakanson et al 1974;Sandvik et al 1987Sandvik et al ,1988. The transmission hypothesis currently enjoys considerable support, but the two mechanisms are not mutually exclusive and the relative dominance of one or other almost certainly differs between species.…”