Regulation of Na+/H+ exchange in opossum kidney cells by parathyroid hormone, cyclic AMP and phorbol esters.
Parathyroid hormone (PTH) controls two proximal tubular brush border membrane transport systems, Na+/phosphate co-transport and Na+/H+ exchange. In OK cells, a cell line with proximal tubular transport characteristics, PTH acts via kinase C and kinase A activation to inhibit Na+/phosphate co-transport [6, 8, 9, 19, 22]. In the present study, we show that PTH inhibits Na+/H+ exchange and that this effect can be mimicked by pharmacological activation of kinase A and kinase C. Ionomycin-dependent increases in cytoplasmic Ca2+ concentration do not induce inhibition of Na+/H+ exchange; PTH-dependent inhibition of Na+/H+ exchange is not prevented by ionomycin or by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (Ca2+ clamping). Detailed dose-response curves for the different agonists, given either alone or in combination, suggest that the two regulatory cascades (kinase A and kinase C) are operating independent of each other and reach a common final target, resulting in 40-50% inhibition of Na+/H+ exchange. An analysis of intracellular pH sensitivity of Na+/H+ exchange suggests that inhibition is not related to a shift in set point, but is rather explained by a reduced Vmax of Na+/H+ exchange and/or reduced affinity for protons at the internal membrane surface. It is suggested that kinase A as well as kinase C can mediate PTH inhibition of renal proximal tubular Na+/H+ exchange and that the relative importance of a particular regulatory cascade is determined by the PTH-concentration-dependent rates in the liberation of diacylglycerol (phospholipase C/kinase C) and cAMP (adenylate cyclase/kinase A).
Helmle-Kolb
C
C
Department of Physiology, University of Zurich, Switzerland.
Montrose
M H
MH
Stange
G
G
Murer
H
H
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology*; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009893:Opossums / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D010281:Parathyroid Hormone; D010703:Phorbol Esters; D010710:Phosphates; D006859:Hydrogen; D012964:Sodium; D000242:Cyclic AMP