Pancreatic secretagogues regulate somatostatin binding to its receptors on rat pancreatic acinar membranes.

Abstract

Labeled somatostatin binding to pancreatic acinar membranes was examined to investigate how pancreatic secretagogues regulate somatostatin receptors in the pancreas. Pretreatment of pancreatic acini at 37 degrees C for 120 min with not only pancreatic secretagogues, such as carbachol and bombesin, but also vasoactive intestinal peptide (VIP) and secretin reduced subsequent labeled somatostatin binding to the acinar membranes in a dose-dependent manner. The inhibitory effects of these secretagogues on labeled somatostatin binding were also time dependent. Both types of secretagogues maximally reduced subsequent somatostatin binding when acini were incubated with them for more than 120 min. However, the degree of the inhibition was greater with carbachol or bombesin than VIP or secretin; the former secretagogues reduced the binding to 40-45%, and the latter to 75-80% of a control, respectively. These pancreatic secretagogues had no inhibitory effect on somatostatin binding when added directly to the binding media. Furthermore, the inhibitory effect of carbachol was attenuated by the presence of 1 mM EDTA in media for pretreatment, suggesting that intracellular pathways activated by pancreatic secretagogues may be responsible for somatostatin receptor modulation. Interestingly, when combined with VIP, pretreatment of acini with carbachol produced an additive inhibition of labeled somatostatin binding to the membranes. Results, therefore, suggest that somatostatin binding to its receptors in the pancreas may be regulated via two functionally distinct intracellular pathways.