The somatostatin/histaminic pathway balance on gastric secretion could be based on a competitive antagonism

Measurements of acid and pepsin secretions and of histamine release in response to food alone or in combination with graded doses of antramine (AH), a molecular form of histamine isolated from antral mucosa, with or without somatostatin were performed simultaneously in dogs equipped with a denervated pouch. AH restored somatostatin-inhibited acid and pepsin secretions but with different intensities in regard to the different inhibitory levels induced by somatostatin. AH competitively antagonized somatostatin (1 microgram/kg/h) inhibition of acid secretion, but when stronger levels of inhibition were achieved, AH restored weakly acid secretion. Recovery of pepsin secretion occurred through a competitive mechanism between AH and somatostatin (1 and 2 micrograms/kg/h). There was a close relationship between the secretory outputs and the integrated histamine responses; the slopes of the regression lines might be considered as reflecting the stimulatory activity of blood histamine on secreting cells. For acid secretion, this activity is similar in control and somatostatin (1 microgram/kg/h) tests, while for pepsin secretion it is identical in control and 1 or 2 micrograms/kg/h somatostatin tests. One can speculate that the suppression of the somatostatin inhibitory effects by antramine, within the limits of physiological conditions, results from a competitive mechanism.