The results suggest that gastrin stimulates acid secretion by releasing histamine from ECL cells. Vagally induced acid secretion is also dependent on a histaminergic pathway but not on ECL-cell histamine.

Rat gastric mucosal cells, containing 25-35% parietal cells, were obtained by a modified isolation procedure involving protease, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and mechanical treatments. Parietal cell responsiveness to secretagogues was assessed by the accumulation of the weak base [14C]aminopyrine in intracellular acidic compartments. Histamine, without phosphodiesterase inhibitors, dose dependently stimulated aminopyrine accumulation with an effective concentration producing 50% of maximal response of 13 microM and a maximal effective dose of 100 microM. Pentagastrin and rat gastrin-17 alone were ineffective but potentiated dose dependently the action of 100 microM histamine. The mean potentiating effect varied from 32 to 70% for 100 nM pentagastrin and from 36 to 95% for 100 nM rat gastrin-17. Pentagastrin (100 nM) also potentiated the effect of 1 mM dibutyryladenosine 3',5'-cyclic monophosphate (cAMP) by 44%, but it did not increase further the stimulation by carbachol. The potentiating effect of pentagastrin on histamine- and dibutyryl cAMP-stimulated aminopyrine accumulation was also observed after enrichment of parietal cells to 65-85%. The endogenous histamine was insufficient to stimulate acid production. Therefore gastrin appears to have a direct action also in rat parietal cells.

The role of endogenous adenosine 3',5'-cyclic monophosphate (cAMP) in the mechanisms of action of gastrin and carbachol on aminopyrine accumulation in isolated pig and rat parietal cells was investigated. In pig cells, pentagastrin (100 nM) alone stimulated aminopyrine accumulation, an action significantly reduced by the protein kinase A inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMP[S]; 100 microM). In rat cells, gastrin-17 (100 nM) was incapable of stimulating aminopyrine accumulation, but it potentiated the action of histamine (100 microM). Carbachol (10 microM) stimulated aminopyrine accumulation and potentiated the action of histamine, and its action was potentiated in a dose-dependent manner by Sp-adenosine 3',5'-cyclic monophosphothioate (Sp-cAMP[S]; a cAMP analogue) in both species. The effect of carbachol was dose dependently reduced by Rp-cAMP[S]. The basal cAMP in pig parietal cells was 3.5-fold higher than that in rat parietal cells. Histamine (100 microM) and 3-isobutyl-1-methylxanthine (IBMX; 100 microM) only slightly elevated the cAMP content (1.2- to 2.9-fold the basal level) in both pig and rat parietal cells. Their combination, however, increased the cAMP level by 8- to 38-fold, but it did not increase aminopyrine accumulation above that elicited by histamine alone. Gastrin did not alter the cAMP levels in parietal cells of either of the two species. Both gastrin and carbachol increased cytosolic free Ca2+ in enriched pig and rat parietal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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