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 (Vbl) with microelectrodes. Pancreatic ducts were dissected from pancreas of normal rats and bathed in a HCO(3-)(-containing solution. Under control conditions, the average Vbl was between -50 and -70 mV. Vasoactive intestinal peptide (VIP) and carbachol (CCH) reversibly depolarized Vbl when applied to the bath. VIP (9 x 10(-9) mol/l) depolarized Vbl 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 depolarization of Vbl, 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 Vbl 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; Vbl depolarized from about -65 mV to -29 mV and the effect was reversible. Substance P (2 x 10(-7) mol/l), alone or in combination with secretin, had no effect on Vbl of the tested duct cells (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)