Somatostatin receptor-effector system in rat pancreatic acinar membranes after subtotal enterectomy.

In the present study we found that exocrine pancreatic hyperplasia observed after proximal small bowel resection is accompanied by an increase in pancreatic somatostatin (SS) content at 1 mo and an increase in the number of SS receptors at 2 wk and 1 mo after intestinal surgery. At 6 mo after small bowel resection SS content and SS receptors had returned to control values. However, the original increase in SS receptor number was accompanied by a decrease in the ability of SS to inhibit forskolin-stimulated adenylyl cyclase (AC) activity. In addition, the ability of 5'-guanylylimidodiphosphate (a nonhydrolyzable GTP analogue) to inhibit SS receptor binding was decreased in pancreatic acinar membranes from enterectomized rats at 2 wk and 1 mo after jejunoileal resection. These data suggest that there is an abnormality in the integrity of SS receptor binding site-G protein interactions and would explain the decreased inactivation of AC by SS at 2 wk and 1 mo after proximal small bowel resection.

Adenylate cyclase activity during exocrine pancreatic proliferation in the rat.

Adenylate cyclase activity in pancreatic acinar cell membranes was determined in rats that had undergone a treatment with pentagastrin (250 micrograms/kg, intraperitoneal three times daily) for 1 week or that had undergone small bowel resection (90%) and were sacrified at 2 weeks, 1 month and 6 months after intervention. Both treatments are potent stimulators of pancreatic acinar cell proliferation. Adenylate cyclase activity was similar under basal conditions and after the diterpene forskolin stimulation in pancreatic acinar membranes from all groups studied. The ability of low concentrations of the stable GTP analogue, 5'-guanylylimidodiphosphate (Gpp[NH]p) to inhibit forskolin-stimulated adenylate cyclase activity was decreased in pancreatic acinar membranes from enterectomized rats at 2 weeks and 1 month after the operation and returned to control values at 6 months after enterectomy. Stimulation of adenylate cyclase by high concentration of Gpp[NH]p or by secretin (10(-8) M) was higher in both pancreatic hyperplasia conditions as compared with control animals. These findings suggest that the coupling efficiency of the Gs protein to adenylate cyclase from pancreatic acinar membranes is enhanced without any alterations in the catalytic activity of the enzyme during pancreatic proliferation. In addition, it is possible that the highly regulated pancreatic acinar adenylate cyclase activity may be necessary to regulate pancreatic acinar cell proliferation.