Beta-adrenergic regulation of cyclic adenosine 3',5' monophosphate accumulation in human gastric epithelial glands. Inhibitory effect of somatostatin.

The action of catecholamines and somatostatin on cyclic adenosine 3',5' monophosphate (cyclic AMP) formation in human isolated gastric glands is reported. We show that: (1) there is a beta 2 receptor-mediated stimulation of cyclic AMP production in fundus. Catecholamines act with the order of potencies isoproterenol (ED50 = 50 nmol 1(-1) greater than epinephrine (ED50 = 0.1 mumol 1(-1] greater than norepinephrine (ED50 = 5 mumol 1(-1]. Their action is completely reversed by propranolol at doses 10(3) times lower than practolol, while unaffected by phentolamine; (2) isoproterenol and Vasoactive Intestinal Peptide (VIP) have additive effects on cyclic AMP in fundic glands whereas no additivity is observed between histamine and isoproterenol; this, together with the absence of catecholamine effect in antral glands, suggests that the beta 2 receptor is located on parietal cells; (3) somatostatin (1 mumol 1(-1] non-competitively inhibits the stimulation by catecholamines but does not affect VIP and histamine stimulations. These results suggest a physiological stimulatory effect of catecholamines on gastric acid secretion in man, through a beta 2 receptor coupled to the cyclic AMP system, regulated by somatostatin.