BACKGROUND & AIMS: In the intact pancreas, bicarbonate secretion is thought to be controlled by a number of regulators, including adrenergic agonists. The aim of this study was to investigate the effects of adrenergic agonists on pancreatic ducts, which are the site of bicarbonate secretion. METHODS: Small intralobular ducts were isolated from rat pancreas and studied in vitro by the whole-cell patch clamp technique. Cell membrane voltages and currents were indicators of cellular ion transport. In some ducts, intracellular Ca2+ activity was measured by fluorescence optical methods. RESULTS: Unstimulated duct cells had a membrane voltage (Vm) of about -50 mV. Isoproterenol had a concentration-dependent effect on Vm; at 10(-7) mol/L, it depolarized Vm by 20-25 mV and the cell conductance increased by 100 nanosiemens. These effects were a result of opening of luminal Cl- channels. Phenylephrine had much smaller effects. At comparable concentrations, it depolarized Vm by a few millivolts. Neither agonist had significant effects on intracellular Ca2+. CONCLUSIONS: This study provides the first direct evidence that adrenergic stimulation, namely, that of beta-adrenoceptors, controls ion transport in pancreatic ducts. Similar to secretin, isoproterenol stimulation leads to opening of luminal Cl- channels, and HCO3- enters the lumen in exchange for Cl-.