Effect of vasoactive intestinal peptide,carbachol and other agonists on the membrane voltage of pancreatic duct cells

The regulation of pancreatic exocrine secretion involves hormonal, neural and neurohormonal components. Many agonists are known to be effective in pancreatic acinar cells, but less is known about the ducts. Therefore, we wanted to investigate the influence of various agonists on isolated perfused pancreatic ducts and, as a physiological response, we 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 intestinal peptide (VIP) and carbachol (CCH) reversibly depolarized V_bl when applied to the bath. VIP (9×10^–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±4mV (n=10). Furthermore, a decrease of the Cl^– concentration in the lumen led to an increase of VIP-induced depolarization of V_bl, suggesting that a luminal Cl^– conductance was increased. 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 cells tested in our preparation (n=7, 6). Neurotensin (10^–8 mol/l) had a marked depolarizing effect in two out of ten cases; V_bl depolarized from about -65 mV to-29 mV and the effect was reversible. Substance P (2×10^–7 mol/l), alone or in combination with secretin, had no effect on V_bl of the tested duct cells (n=11). We propose that the basolateral membrane of pancreatic duct cells possesses receptors for VIP, acetylcholine and neurotensin. CCK, bombesin and substance P had no detectable effects on V_bl of the duct cells tested, which could 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.Preliminary reports of the present study were presented at the 70th and 71st Meetings of the German Physiological Society, Germany, September 1991, March 1992