Human brain capillary endothelium: modulation of K+ efflux and K+, Ca2+ uptake by endothelin.
This report describes K+ efflux, K+ and Ca2+ uptake responses to endothelins (ET-1 and ET-3) in cultured endothelium derived from capillaries of human brain (HBEC). ET-1 dose dependently increased K+ efflux, K+ and Ca2+ uptake in these cells. ET-1 stimulated K+ efflux occurred prior to that of K+ uptake. ET-3 was ineffective. The main contributor to the ET-1 induced K+ uptake was ouabain but not bumetanide-sensitive (Na+-K+-ATPase and Na+-K+-Cl- cotransport activity, respectively). All tested paradigms of ET-1 effects in HBEC were inhibited by selective antagonist of ET(A) but not ET(B) receptors and inhibitors of phospholipase C and receptor-operated Ca2+ channels. Activation of protein kinase C (PKC) decreased whereas inhibition of PKC increased the ET-1 stimulated K+ efflux, K+ and Ca2+ uptake in HBEC. The results indicate that ET-1 affects the HBEC ionic transport systems through activation of ET(A) receptors linked to PLC and modulated by intracellular Ca2+ mobilization and PKC.
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4128, USA.
M
M
Spatz
N
N
Kawai
J
J
Bembry
F
F
Lenz
R M
RM
McCarron
D001921:Brain / Q000098:blood supply / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002196:Capillaries / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D019334:Endothelin-3 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008301:Maleimides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D002121:Calcium Channel Blockers; D019332:Endothelin-1; D019334:Endothelin-3; D016232:Endothelins; D007211:Indoles; D008301:Maleimides; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000254:Sodium-Potassium-Exchanging ATPase; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium