Inositol 3,4,5,6-tetrakisphosphate specifically inhibits a
receptor-mediated, ca2+-dependent cl- current in cfpac-1 cells.
Ho, Melisa W. Y., Stephen B. Shears, Karol S. Bruzik, Marek Duszyk,
and Andrew S. French.
Department of Physiology, University of Alberta, Edmonton, Alberta,
Canada T6G 2H7; Laboratory of Cellular and Molecular Pharmacology,
National Institute of Environmental Health, Research Triangle Park,
North Carolina 27709; Department of Medicinal Chemistry and
Pharmacognosy, University of Illinois at Chicago, 833 South Wood St.,
Chicago Illinois 60516; Department of Physiology and Biophysics,
Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7
APStracts 3:0353C, 1996.
We have examined the role of Ins(3,4,5,6)P4 in the control of Cl-
current in CFPAC-1 cells. Intracellular Ins(3,4,5,6)P4 had no effect
on basal current, but it produced a 5-7 fold reduction in the Cl-
current stimulated by either 2?[mu]M extracellular ATP or by 1?[mu]M
extracellular thapsigargin. The half-maximally effective dose of
Ins(3,4,5,6)P4 was 2.9 [mu]M, while 4 [mu]M blocked >80% of
the ATP-activated current. In contrast, 10 [mu]M of Ins(1,4,5,6)P4,
Ins(1,3,4,5)P4 or Ins(1,3,4,6)P4 enhanced rather than inhibited the
ATP-activated Cl- current, although Ins(1,4,5,6)P4 only acted
transiently. These stimulatory effects were Ca2+-dependent and
largely inhibited by co-application of equimolar Ins(3,4,5,6)P4.
Ins(1,3,4,5,6)P5, the precursor of Ins(3,4,5,6)P4, did not affect Cl-
current. These data consolidate and extend the hypothesis that
Ins(3,4,5,6)P4 is an important intracellular regulator of Cl- current
in epithelial cells.
Received 10 April 1996; accepted in final form 8 October 1996.
APS Manuscript Number C196-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996