EVIDENCE FOR AUTOREGULATION OF CHOLECYSTOKININ SECRETION DURING DIVERSION OF BILE PANCREATIC-JUICE IN RATS

Background & Aims: The mechanism regulating cholecystokinin (CCK) secretion during prolonged diversion of bile pancreatic juice (BPJ) is unknown. We examined the hypothesis that the decrease of plasma CCK levels after prolonged diversion of BPJ is mediated by an increase in plasma somatostatin levels evoked by hypercholecystokinemia and somatostatin in turn inhibits CCK-releasing peptide (CCK-RP) bioactivity and decreases plasma CCK levels. Methods: Pancreatic secretion, plasma CCK levels, and somatostatin levels were monitored for 7 hours after diversion of BPJ in anesthetized rats. Secretion of CCK-RP bioactivity during diversion of BPJ was examined in the presence or absence of somatostatin. Results: Diversion of BPJ for 2 hours caused a 13- and 2.5-fold increase in plasma CCK and somatostatin levels. The increase in somatostatin levels was blocked by the CCK antagonist L364,718. At 5 hours after diversion of BPJ, plasma CCK and somatostatin levels and luminal CCK-RP bioactivity decreased to basal levels. The decrease in plasma CCK levels was prevented by the administration of a specific somatostatin antagonist. We also showed that the stimulatory effect of the CCK-RP bioactivity was eliminated when the donor rat was pretreated with somatostatin. Conclusions: Autoregulation of CCK secretion occurs during the diversion of BPJ and this is mediated by somatostatin, which inhibits the secretion of CCK-RP bioactivity and decreases plasma CCK levels.