INHIBITION BY SOMATOSTATIN OF AMYLASE SECRETION INDUCED BY CALCIUM AND CYCLIC-AMP IN RAT PANCREATIC ACINI

It has recently been shown that somatostatin inhibits amylase secretio n from isolated pancreatic acini by reducing cyclic AMP (cAMP) product ion [Matsushita, Okabayashi, Hasegawa, Koide, Kido, Okutani, Sugimoto and Kasuga (1993) Gastroenterology 104, 1146-1152]. To date, however, little is known as to the other mechanism(s) by which somatostatin inh ibits amylase secretion in exocrine pancreas. To investigate the actio n of somatostatin independent of cAMP generation, we examined the effe ct of somatostatin in isolated rat pancreatic acini stimulated by 1 mu M calcium ionophore A23187 and 1 mM 8-bromo-cyclic AMP (8Br-cAMP). So matostatin inhibited amylase secretion evoked by a combination of A231 87 and 8Br-cAMP in a dose-dependent manner. The maximum inhibition was obtained by 10(-7) M somatostatin, and at this concentration somatost atin inhibited the effect of A23187 and 8Br-cAMP by approximately 30%. In electrically permeabilized acini, an elevation of free calcium con centration resulted in an increase in amylase secretion and cAMP enhan ced the secretion evoked by calcium. cAMP shifted the dose-response cu rve for calcium-induced secretion leftwards and elevated the peak valu e of secretion. Somatostatin inhibited the effect of cAMP on calcium-i nduced amylase secretion by shifting the dose-response curve to the ri ght. To determine the involvement of a G-protein(s), we examined the e ffect of somatostatin in acini pretreated with pertussis toxin. Pretre atment of acini with pertussis toxin completely blocked somatostatin-i nhibition of amylase-secretion evoked by A23187 and 8Br-cAMP. These re sults indicate that somatostatin decreases amylase secretion induced b y cAMP and calcium by reducing the calcium sensitivity of exocytosis. A pertussis toxin-sensitive G-protein is also involved in this step.