Intracellular cascades in the parathyroid-hormone-dependent regulation of Na+/phosphate cotransport in OK cells.
Parathyroid hormone (PTH) increased intracellular cyclic AMP and reduces Na+/phosphate cotransport activity in OK cells [Malmström & Murer (1986) Am. J. Physiol. 251, C23-C31; Caverzasio, Rizzoli & Bonjour (1986) J. Biol. Chem. 261, 3233-3237]. It was also shown that PTH activates phosphoinositide metabolism in OK cells [Hruska, Moskowitz, Esprit, Civitelli, Westbrook & Huskey (1987) J. Clin. Invest. 79, 230-239]. In the present paper we show that tumour-promoting phorbol esters are effective in reducing Na+/phosphate cotransport. The Ca2+ ionophores A23187 and ionomycin had only a small effect on Na+/phosphate cotransport; added together, A23187 and phorbol esters showed a synergistic action. Phorbol esters and phorbol esters plus ionomycin stimulated prostaglandin synthesis as well as cyclic AMP production; acetylsalicylic acid prevented phorbol-ester-induced prostaglandin synthesis and cyclic AMP production, but had no effect on inhibition of Na+/phosphate cotransport. In suspensions of OK cells, PTH and thrombin produced a rise in intracellular Ca2+. In contrast with PTH, thrombin did not elevate cellular cyclic AMP in suspended OK cells. PTH and thrombin reduced Na+/phosphate cotransport in suspended OK cells. It is suggested that two regulatory cascades are involved in PTH action on Na+/phosphate cotransport: cyclic AMP/kinase A and Ca2+/diacylglycerol/kinase C.
Malmström
K
K
Department of Physiology, University of Zurich, Switzerland.
Stange
G
G
Murer
H
H
D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D015232:Dinoprostone; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
D004075:Diglycerides; D007476:Ionophores; D010281:Parathyroid Hormone; D010703:Phorbol Esters; D010710:Phosphates; D011458:Prostaglandins E; C038237:1-oleoyl-2-acetylglycerol; D012964:Sodium; D000242:Cyclic AMP; D013917:Thrombin; D015232:Dinoprostone; D002118:Calcium