Stimulation of Na+/H+ exchange activity by endothelin in opossum kidney cells.
Endothelin-1 (ET-1) controls multiple aspects of kidney function. In this study we have analysed the effects of ET-1 on apical Na+/H+ exchange activity in opossum kidney (OK) cells. ET-1 (at 10(-10) M and 10(-8) M) activated Na+/H+ exchange activity within 5 min of exposure. ET-1 (10(-8) M) prevented PTH-induced (parathyroid hormone; 10(-8) M) inhibition of Na+/H+ exchange activity; it also abolished transport inhibition in response to 10(-3) M IBMX (isobutyl-methylxanthine) and 3 x 10(-7) M TPA (phorbol 12-myristate 13-acetate), but had no effect on the 8-bromo-cAMP-induced (10(-4) M) decrease of transport rate. Basal cAMP content, IBMX- and PTH-stimulated cAMP production were unaffected by ET-1 (10(-8) M). The stimulatory action of ET-1 (10(-8) M) on Na+/H+ exchange activity was prevented by calphostin C (10(-8) M). These data document that OK cells might serve as a useful in vitro model for analysis of cellular mechanisms involved in endothelin action; proteine kinase C activation seems to participate in the observed endothelin effects.
Walter
R
R
University of Zürich, Institute of Physiology, Switzerland.
Helmle-Kolb
C
C
Forgo
J
J
Binswanger
U
U
Murer
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D017136:Ion Transport; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D009893:Opossums; D010281:Parathyroid Hormone / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016232:Endothelins; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D010281:Parathyroid Hormone; D017923:Sodium-Hydrogen Exchangers; C061465:calphostin complex; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine