Elevated extracellular K+ enhances arachidonic acid release in MDCK-D1 cells.
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.
Howard
M J
MJ
Department of Pharmacology, University of California, San Diego, La Jolla 92093.
Insel
P A
PA
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D008555:Melitten / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D008555:Melitten; D016718:Arachidonic Acid; D000001:Calcimycin; D015232:Dinoprostone; D011188:Potassium; D002118:Calcium; D011224:Prazosin; D004837:Epinephrine