ADENYLATE-CYCLASE ACTIVITY DURING EXOCRINE PANCREATIC PROLIFERATION IN THE RAT

Adenylate cyclase activity in pancreatic acinar cell membranes was det ermined in rats that had undergone a treatment with pentagastrin (250 mu g/kg, intraperitoneal three times daily) for 1 week or that had und ergone small bowel resection (90%) and were sacrified at 2 weeks, 1 mo nth and 6 months after intervention. Both treatments are potent stimul ators of pancreatic acinar cell proliferation. Adenylate cyclase activ ity was similar under basal conditions and after the diterpene forskol in stimulation in pancreatic acinar membranes from all groups studied. The ability of low concentrations of the stab le GTP analogue, 5'-gua nylylimidodiphosphate (Gpp[NH]p) to inhibit forskolin- stimulated aden ylate cyclase activity was decreased in pancreatic acinar membranes fr om 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 com pared with control animals. These findings suggest that the coupling e fficiency of the G(s) protein to adenylate cyclase from pancreatic aci nar membranes is enhanced without any alterations in the catalytic act ivity of the enzyme during pancreatic proliferation. In addition, it i s possible that the highly regulated pancreatic acinar adenylate cycla se activity may be necessary to regulate pancreatic acinar cell prolif eration.