Nucleotide-receptor mediated decrease of tight-junctional permeability in cultured human cervical epithelium. Gorodeski, George I., Dirk E. Peterson, Brian J. De Santis, and Ulrich Hopfer. Departments of Reproductive Biology and Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio
APStracts 2:0413C, 1995.
Extracellular ATP changes the transepithelial electrical conductance (GT) across cultures of human cervical cells acutely, in a biphasic manner that is characterized by a rapid increase (Phase-I) followed by a sustained decrease in GT (Phase-II). We tested the hypothesis that the Phase-II response is mediated by decreases in the permeability of tight junctions. We studied the effect of ATP on the relative mobilities of Cl- versus Na+ (uCl/uNa) as calculated from changes in the dilution potential (Vdil). Vdil was induced by lowering NaCl from 130 mM to 10 mM in either the luminal or subluminal solutions bathing filters containing cells. uCl/uNa was 1.27 across cervical cultures and 1.34 across blank filters, compared to a level of 1.52 in free solution. Increases in GT induced by transepithelial hydrostatic or hypertonic gradients (which increase the permeability of the lateral intercellular space) had no effect on uCl/uNa. Increases in G T induced by lowering extracellular calcium to &LT0.1 mM increased uCl/uNa to levels obtained in blank filters, indicating abrogation of tight-junctional resistance. Phase -I response and ionomycin (which produces a sustained Phase-I-like increase in GT) had no effect on uCl/uNa. The Phase-II response, however, decreased u Cl/u Na from 1.27 to 1.24, and the effect could be abrogated by lowering extracellular calcium. These results indicate that Phase-II decreases in GT across cultured human cervical epithelium are mediated by acute decreases in tight-junctional permeability. 

Received 14 July 1995; accepted in final form 16 November 1995.
APS Manuscript Number C425-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95