Potentiation of regulatory volume decrease by p2u purinoceptors in hsg-pa cells. Kim, Hyun Dju, Jesse W. Bowen, Marilyn R. James-Kracke, Linda A. Landon, Jean M. Camden, Jane E. Burnett, and John T. Turner. Department of Pharmacology, School of Medicine, University of Missouri, Columbia, MO 65212 USA, phone: (314) 882-7186, FAX: (314) 884-4558
APStracts 2:0238C, 1995.
HSG-PA human salivary gland duct cells exhibit progressively increased regulatory volume decrease (RVD) in response to decreased medium osmolarity. The P2U purinoceptor agonist UTP causes a potentiation of RVD, the extent of which is most pronounced in 220 mOsm medium and is least apparent in 180 mOsm medium. We examined the underlying mechanisms for this effect. Exposure of HSG-PA cells to UTP promotes Ca2- mobilization, hyperpolarization and net K efflux, suggesting the participation of Ca2--activated K channels in RVD. To delineate the anion counterpart of K movement during RVD, cell swelling in the presence of gramicidin, which abolishes the membrane potential, was measured. In response to a sudden dilution in hypotonic media, gramicidin-treated cells swelled immediately, followed by a "secondary swelling" in 180 mOsm but not in 220 mOsm medium. The results suggest that in 180 mOsm cells perform spontaneous RVD mediated by increased anion conductance. In 220 mOsm medium where RVD is minimal, the increase in anion conductance is marginal. In our model of RVD in which cells were challenged by UTP, the ensuing hyperpolarization provides the driving force for net Cl efflux, which is confirmed by tracer flux studies during purinoceptor-activated RVD. Thus, RVD, which has long been regarded as a self-sufficient cellular program, appears to be subject to extracellular control in HSG-PA cells through receptor-mediated processes.

Received 23 March 1995; accepted in final form 22 June 1995.
APS Manuscript Number C164-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  6 July 1995.