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.