Characterization of the activation of Na+/H+ exchange in lymphocytes by phorbol esters: change in cytoplasmic pH dependence of the antiport.
Phorbol 12-myristate 13-acetate and other phorbol esters induce an intracellular alkalinization in rat thymic lymphocytes. An extracellular acidification can be recorded concomitantly. This transmembrane H+ (equivalent) flux is dependent on external Na+ and is amiloride sensitive. Phorbol esters also stimulate an amiloride-sensitive uptake of 22Na+, suggesting activation of Na+o/H+i exchange. Only those phorbol derivatives that are tumor promoters and activators of protein kinase C stimulate the antiport. Activation of the Na+/H+ exchange is brought about by a change in the cytoplasmic pH sensitivity of the antiport. Activation of the Na+/H+ exchanger by phorbol esters results in membrane hyperpolarization, due to indirect stimulation of the electrogenic Na+/K+ pump by the increased intracellular Na+ concentration. Increased Na+/H+ exchange also produces cell swelling, which may be one of the earliest manifestations of the growth-promoting properties of the phorbol esters.
Grinstein
S
S
Cohen
S
S
Goetz
J D
JD
Rothstein
A
A
Gelfand
E W
EW
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008214:Lymphocytes / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D014882:Water-Electrolyte Balance / Q000187:drug effects
D002352:Carrier Proteins; D010703:Phorbol Esters; D010704:Phorbols; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D012964:Sodium; D002118:Calcium