EFFECT OF VASOACTIVE-INTESTINAL-PEPTIDE, CARBACHOL AND OTHER AGONISTSON THE MEMBRANE VOLTAGE OF PANCREATIC DUCT CELLS

The regulation of pancreatic exocrine secretion involves hormonal, neu ral and neurohormonal components. Many agonists are known to be effect ive in pancreatic acinar cells, but less is known about the ducts. The refore, we wanted to investigate the influence of various agonists on isolated perfused pancreatic ducts and, as a physiological response, w e measured the basolateral membrane voltage of the duct cells (V(bl)) with microelectrodes. Pancreatic ducts were dissected from pancreas of normal rats and bathed in a HCO3--containing solution. Under control conditions, the average V(bl) was between -50 and -70 mV. Vasoactive i ntestinal peptide (VIP) and carbachol (CCH) reversibly depolarized V(b l) when applied to the bath. VIP (9 X 10(-9) mol/l) depolarized V(bl) from -72 +/- 3 mV to -53 +/- 3 mV (n = 20) and CCH (10(-5) mol/l) from -62 +/- 3 to -35 +/- 4 mV (n = 10). Furthermore, a decrease of the Cl - concentration in the lumen led to an increase of VIP-induced depolar ization of V(bl), suggesting that a luminal Cl- conductance was increa sed. Cholecystokinin (CCK, 10(-10)-10(-7) mol/l) and bombesin (10(-8), 10(-5) mol/l), which stimulate pancreatic exocrine secretion in acini or whole glands, showed no significant effect on V(bl) of the duct ce lls tested in our preparation (n = 7, 6). Neurotensin (10(-8) mol/l) h ad a marked depolarizing effect in two out of ten cases; V(bl) depolar ized from about -65 mV to -29 mV and the effect was reversible. Substa nce P (2 X 10(-7) mol/l), alone or in combination with secretin, had n o effect on V(bl) of the tested duct cells (n = 11). We propose that t he basolateral membrane of pancreatic duct cells possesses receptors f or VIP, acetylcholine and neurotensin. CCK, bombesin and substance P h ad no detectable effects on V(bl) of the duct cells tested, which coul d be due to the lack of corresponding receptors on these cells, or due to the absence of electrophysiologically detectable effects, in spite of receptor presence.