In morphologically different biopsy specimens from fundic, antral and duodenal mucosa of 134 persons, basal and histamine stimulated adenylate cyclase activity was studied: Basal and stimulated adenylate cyclase activities were log-normally distributed. Only in the fundic but not in the antral and duodenal mucosa adenylate cyclase was sensitive to histamine. The mean basal activity in the fundic gastric mucosa was 148, in response to 10(-5) mol/l histamine 292 pmol cAMP/mg protein/20 min. In human fundic biopsy specimens histologically identified as normal gastric mucosa, the stimulatory effect of histamine on adenylate cyclase decreased with the individual's age. In bioptic material from patients suffering from histologically proven chronic gastritis the histamine effect decreased with the degree of atrophy. A similar loss of histamine sensitivity was found in gastric mucosal biopsies of antrectomized individuals operated at least 5 years before by the Billroth I or II method, whereas in the mucosa of patients with gastric or duodenal ulcer no loss occurred. In contrast, the most pronounced stimulatory action of histamine was found in this latter group. Since a histamine sensitive adenylate cyclase is localized only in the glandular area of the fundic mucosa and the histamine sensitivity depends on a morphological intact structure of the mucosa, it can be concluded, that the effects of histamine on adenylate cyclase and on hydrochloric acid acid secretion have to be considered as a mechanism linked together.

The activity of the non-stimulated, basal adenylate cyclase of the dog gastric mucosa is reduced by the histamine H2-receptor antagonist metiamide but not by the histamine H1-receptor antagonist mepyramine. Histamine activates the adenylate cyclase only slightly. In the presence of 10(-5) M metiamide a concentration-dependent stimulation of the enzyme by histamine was found. These data indicate that endogenous histamine in dog gastric mucosal homogenate is contributing at least in part to what is measured as "basal" adenylate cyclase activity. This effect is mediated by H2-receptor excitation and in earlier studies has prevented the demonstration of a stimulatory effect of exogenous histamine on this enzyme.

Adenylate cyclase (AC) in response to prostaglandin E₂ (PGE₂) and histamine was studied in morphologically different biopsy specimens from human gastric mucosa. The activities of the enzyme were log-normally distributed and did not differ between males and females. PGE₂ activated AC in a concentration-dependent manner in normal gastric mucosa (n = 57), chronic superficial gastritis (GI, 18), chronic gastritis with beginning atrophy (GII, 10), chronic atrophic gastritis (GUI, 24), gastric ulcer (GU, 39), duodenal ulcer (DU, 32), and biopsies of patients operated according to Billroth II (BII, 20) and was most efficacious in GUI and BII. Histamine, which was studied in normal gastric mucosa (n = 27), DU (n = 20), GU (n= 13), and BII (n = 18), stimulated AC most efficaciously and potently in DU, was less effective in normal gastric mucosa and GU, and had no effect at all in BII. Cimetidine treatment of DU patients did not change the PGE₂ action, while the degree of stimulation by histamine was reduced. The data indicate characteristic differences of the PGE₂- and histamine-sensitive AC in the mucosal samples of these patients.

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