THE EFFECT OF PENTAGASTRIN ON THE SOMATOSTATIN RECEPTOR-EFFECTOR SYSTEM IN RAT PANCREATIC ACINAR MEMBRANES

An intraperitoneal (i.p.) injection of pentagastrin (250 mu g/kg, thre e times daily) for 1 week increased somatostatin like-immunoreactivity (SSLI) content in the pancreas and the number of somatostatin (SS) re ceptors in pancreatic acinar membranes without influencing their appar ent affinity as compared with control animals. No significant differen ces were seen in basal or forskolin (FK)-stimulated adenylate cyclase (AC) enzyme activities in the control and pentagastrin treated rats. I n spite of the increase in the number of SS receptors, SS caused a sig nificantly lower inhibition in AC activity in these membranes. This fi nding is related to the fact that the stable GTP analogue, 5'-guanylyl imidodiphosphate (Gpp[NH]p) was a much less potent inhibitor of bindin g in the pancreatic acinar cell membranes from pentagastrin-treated an imals than in those from controls. In addition the ability of Gpp(NH)p to inhibit FK-stimulated AC activity was also decreased in pancreatic acinar cell membranes from pentagastrin-treated rats. Pretreatment wi th proglumide, (20 mg/kg i.p.) a gastrin/cholecystokinin (CCK) recepto r antagonist, prevented the pentagastrin-induced changes in SS level a nd binding as well as the inhibitory effect of SS on AC activity in pa ncreatic acinar cell membranes. Proglumide alone had no observable eff ect on the somatostatinergic system. These data suggest a SS receptor/ G protein uncoupling as a result of binding of pentagastrin to gastrin receptors present in pancreatic acinar cell membranes.