Actions of palytoxin on na+ and ca2+ homeostasis in human
osteoblast-like saos-2 cells.
Monroe, James J., and Armen H. Tashjian, Jr.
Department of Molecular and Cellular Toxicology, Harvard School of
Public Health, and Department of Biological Chemistry and Molecular
Pharmacology, Harvard Medical School, Boston MA 02115
APStracts 2:0151C, 1995.
Palytoxin (PTx) is a potent membrane-active agent produced by marine
coelenterates which acts to stimulate bone resorption in organ
culture at nanomolar concentrations. We report here the actions of
PTx on Na+ and Ca2+ homeostasis in human osteoblast-like SaOS-2
cells. PTx induced a rise in the cytosolic free Na+ concentration
([Na+]i) by causing entry of extracellular Na+ (Na+e). PTx also
caused a dose-dependent biphasic rise in the cytosolic free Ca2+
concentration ([Ca2+]i) by enhancing entry of extracellular Ca2+
(Ca2+e). Entry of Na+ was dependent on the presence of Ca2+e and was
prevented by the Na+-Ca2+ exchange antagonist 3,4-dichlorobenzamil
(DCB). Entry of Ca2+ was dependent on the presence of Na+e but was
not prevented by DCB. The actions of PTx on [Na+]i and [Ca2+]i were
completely inhibited by pretreatment of the cells with ouabain.
Ouabain alone had no acute effect on [Na+]i or [Ca2+]i in SaOS-2
cells. We propose that interaction of PTx with the Na+ pump created a
channel which allowed influx of Na+e and Ca2+e. The rise in [Ca2+]i
then stimulated the activity of the plasma membrane Na+-Ca2+
exchanger which further enhanced Na+e entry.
Received 31 October 1994; accepted in final form 6 March 1995.
APS Manuscript Number C644-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 March 1995.