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.