Endothelin stimulates Na+/H+ exchange in vascular smooth muscle cells.
The effect of endothelin (ET) on the intracellular pH (pHi) of vascular smooth muscle cells (VSMC), was investigated using a fluorescent pH indicator 2',7'-bis(carboxyethyl)carboxyfluorescein (BCECF). ET at concentrations of over 10(-9) M caused dose-dependent transient acidification followed by Na(+)-dependent and amiloride-sensitive alkalization of the cells due to stimulation of Na+/H+ exchange. The alkalization induced by ET was Ca2(+)-dependent and was inhibited by a calcium channel blocker, nicardipine. Pretreatment with H-7, an inhibitor of protein kinase C, also inhibited the ET-induced cell alkalization. These results indicate that ET stimulates Na+/H+ exchange, resulting in alkalization of VSMC and that this ET-induced cell-alkalization is probably linked to Ca2+ influx and activation of protein kinase C.
Koh
E
E
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Morimoto
S
S
Kim
S
S
Nabata
T
T
Miyashita
Y
Y
Ogihara
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007474:Ion Exchange; D007546:Isoquinolines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012964:Sodium / Q000378:metabolism*
D016232:Endothelins; D007546:Isoquinolines; D010455:Peptides; D010879:Piperazines; D000584:Amiloride; D006859:Hydrogen; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D009529:Nicardipine; D011493:Protein Kinase C; D002118:Calcium