β-adrenergic regulation of ion transport in pancreatic ducts: Patch-clamp study of isolated rat pancreatic ducts

Abstract

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 Ca 2+ activity was measured by fluorescence optical methods. Results: Unstimulated duct cells had a membrane voltage (V m) of about −50 mV. Isoproterenol had a concentration-dependent effect on V m; at 10 −7 mol/L, it depolarized V m 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 V m by a few millivolts. Neither agonist had significant effects on intracellular Ca 2+. Conclusions: This study provides the first direct evidence that adrenergic stimulation, namely, that of β-adrenoceptors, controls ion transport in pancreatic ducts. Similar to secretin, isoproterenol stimulation leads to opening of luminal Cl − channels, and HCO 3 − enters the lumen in exchange for Cl −. GASTROENTEROLOGY 1998;115:714-721