EFFECT OF SOMATOSTATIN AND OCTREOTIDE ACETATE ON OP-CCK-STIMULATED EXOCRINE SECRETION IN THE DENERVATED CANINE PANCREAS

Somatostatin and its analogue, octreotide acetate (Sandostatin), have been demonstrated to suppress exocrine secretion in a denervated canin e pancreatic autograft ft model. To help define this inhibitory mechan ism, the effect of these agents on cholecystokinin (CCK)-stimulated ac inar cell secretion was evaluated. In vitro assessment evaluated the e ffect of somatostatin on octapeptide (OP)-CCK-stimulated amylase relea se of pancreatic tissue slices. In vivo assessment employed animals wi th pancreatic autografts and pancreaticocystostomies. evaluating the e ffect of a bolus intravenous injection of 100 mu g of octreotide aceta te on the basal and OP-CCK-stimulated (125 ng/kg/h) secretion of urina ry (autograft) amylase and bicarbonate. Incubation of tissue slices wi th 0.16, 0.24, or 0.32 mu g/ml somatostatin had no significant effect on in vitro OP-CCK-stimulated amylase release. Intravenous octreotide acetate resulted in a significant decrease in the basal rate of amylas e secretion but had no significant effect on OP-CCK-stimulated autogra ft amylase or bicarbonate release. These studies demonstrate that octr eotide acetate has an in vivo inhibitory effect on basal amylase relea se of pancreatic autografts but cannot counteract maximal stimulation with exogenous OP-CCK. Also, somatostatin does not inhibit OP-CCK-stim ulated acinar cell secretion of pancreatic tissue slices. These result s indicate that the exocrine inhibition produced by somatostatin analo gues in the grafted pancreas occurs via an indirect mechanism.