Stimulation of Na⁺/H⁺ exchange activity by endothelin in opossum kidney cells

Abstract

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 (isobutylmethylxanthine) and 3×10⁻⁷ 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.