DUAL ACTIONS OF GLUCAGON - DIRECT STIMULATION AND INDIRECT INHIBITIONOF DOG PANCREATIC-SECRETION

The secretory actions of glucagon on the exocrine pancreas were examin ed using two kinds of canine preparations. In the isolated and blood-p erfused dog pancreas with venous drainage, i.a. injection of glucagon did not inhibit secretin/cholecysto-kinin-octapeptide (CCK-8)-stimulat ed pancreatic secretion, but instead dose dependently enhanced both ba sal and stimulated pancreatic secretion. Glucagon-induced increase of pancreatic secretion was potentiated by 3-isobutyl-1-methylxanthine. I n contrast, iv. bolus injection of glucagon (3 and 10 nmol/kg) first a ugmented transiently then suppressed secretin/CCK-8-stimulated pancrea tic secretion while simultaneously increasing circulating plasma somat ostatin immunoreactivity from 14.2 to 214 fmol/ml in anesthetized inta ct dogs. The inhibition of secretin/CCK-8-stimulated pancreatic secret ion and elevation of plasma somatostatin immunoreactivity induced by g lucagon were comparable with those due to somatostatin-14. Thus, these results indicate that glucagon stimulates pancreatic secretion direct ly; the inhibitory action of glucagon is indirect and appears to be re lated to a rise in the circulating level of somatostatin immunoreactiv ity.