AJP - Cell Physiology, Vol 259, Issue 2 C224-C231, Copyright © 1990 by American Physiological Society
Elevated extracellular K+ enhances arachidonic acid release in MDCK-D1 cells
M. J. Howard and P. A. Insel
Department of Pharmacology, University of California, San Diego, La Jolla 92093.
Depolarization can alter the expression of membrane receptors and change
certain receptor-mediated events, but previous studies have not assessed
the impact of depolarization on generation of arachidonic acid and its
metabolites (AA) in nonexcitable tissues. We assessed AA generation in
Madin-Darby canine kidney (MDCK) cells grown for 3 days in increased
extracellular [K+], which is known to acutely depolarize these cells.
Growth under these conditions resulted in decreases in the number of alpha
1-adrenergic receptors (alpha 1 AR), a small decrease in receptor-mediated
phosphoinositide hydrolysis, but increases in alpha 1 AR-mediated
prostaglandin E2 formation and AA release. Calcium ionophore (A23187)-,
melittin-, and bradykinin-stimulated AA release were also enhanced. The
reduction in alpha 1 AR number and increased AA release were substantially
reduced or eliminated when K(+)-treated cells were grown in the absence of
extracellular calcium. The results provide evidence that hormone-stimulated
AA release and prostaglandin production can be enhanced by chronic exposure
to elevated extracellular K+ concentration, perhaps as a consequence of a
depolarization-induced enhancement in phospholipase A2 activity. The
results provide evidence for the parallel and independent regulation of the
pathways for receptor-mediated phosphoinositide hydrolysis (phospholipase C
activation) and AA release (phospholipase A2 activation) in MDCK cells.
