SOMATOSTATIN INHIBITS PANCREATIC-ENZYME SECRETION AT A CENTRAL VAGAL SITE

The mechanisms and site of action of somatostatin-induced inhibition o f pancreatic enzyme secretion were investigated using different stimul ants of pancreatic secretion acting on different sites in anesthetized rats. Administration of graded doses of somatostatin-14 resulted in a dose-related inhibition of pancreatic protein secretion evoked by 2-d eoxy-D-glucose, a central vagal stimulant that acts by stimulating the dorsal vagal nuclei. The lowest effective dose of somatostatin-14 was 1.0 mug.kg-1.h-1; maximal effective dose was 25 mug.kg-1.h-1, which r esulted in complete inhibition of protein output. Similarly, somatosta tin-14 at a dose of 25 mug.kg-1.h-1 also completely inhibited pancreat ic protein secretion in response to a physiological concentration of c holecystokinin octapeptide (CCK-8), which acts via a vagal afferent pa thway. In contrast, pancreatic protein outputs evoked by bethanechol, which directly stimulates pancreatic muscarinic receptors, or electric al stimulation of the vagal trunk, which activates the vagal efferent pathway, were unaffected by somatostatin-14. In separate studies, we d emonstrated that perivagal treatment with the sensory neurotoxin capsa icin impaired pancreatic responses to CCK-8 but had no effect on the i nhibitory action of somatostatin-14 on pancreatic secretion evoked by 2-deoxy-D-glucose, ruling out an effect of somatostatin on the vagal a fferent pathway. Similarly we also demonstrated that perineural capsai cin treatment of the celiac-superior mesenteric ganglia did not affect the inhibitory action of somatostatin. These findings indicate that s omatostatin inhibits 2-deoxy-D-glucose- and CCK-8-evoked pancreatic en zyme secretion via a vagal pathway. Somatostatin acts on neither the p eripheral vagal afferent or efferent pathway nor directly on the pancr eatic acini but instead exerts its inhibitory action at a central vaga l site.