Inhibition of phosphatidylinositide 3-kinase in OK-cells reduces Na/P-i-cotransport but does not interfere with its regulation by parathyroid hormone

The importance of phosphatidylinositide 3-kinase(s) [PI 3-kinase(s)] in mem brane trafficking processes led us to examine its/their possible role in pa rathyroid-hormone- (PTH-) induced endocytosis and lysosomal degradation of the type IIa Na/P-i-cotransporter in opossum kidney cells (OK-cells). We us ed wortmannin, a potent inhibitor of several mammalian PT 3-kinase isoforms , and measured Na/P-i-cotransporter activity and type IIa Na/P-i-cotranspor ter protein expression; also the induction of a negative dominant subunit ( Delta p85) was used to reduce PI 3-kinase activity. Wortmannin and Delta p8 5 led to a reduction of Na/P-i-cotransport activity but were unable to prev ent its inhibition by PTH. Wortmannin led in a dose- and time-dependent man ner to a reduction of Na/P-i-cotransport activity and transporter protein e xpression, and retarded their recovery from PTH-induced inhibition/degradat ion. The data suggest that a PI 3-kinase "controlled" mechanism is involved in the synthesis (and/or routing) of the apical type IIa Na/P-i-cotranspor ter in OK-cells.