ANGIOTENSIN II-DEPENDENT PROXIMAL TUBULE SODIUM-TRANSPORT IS MEDIATEDBY CAMP MODULATION OF PHOSPHOLIPASE-C

Angiotensin II (ANG II) stimulates proximal tubule sodium transport by decreasing adenylyl cyclase activity. The role of ANG II-dependent ph ospholipase C is less certain. To determine the contribution of phosph olipase C and adenylyl cyclase to apical (AP) ANG II-dependent sodium transport, unidirectional (AP to basolateral) Na-22 flux was measured in rat proximal tubule cells cultured on permeable supports. AP ANG II (100 nM)-dependent sodium flux was prevented by preincubation with co ncentrations of the phospholipase C inhibitor U-73122 (1 mu M) that bl ocked ANG II-dependent inositol phosphate formation. AP ANG II-depende nt sodium flux was also abolished by preincubation with the intracellu lar calcium mobilization inhibitor 3,4,5-trimethoxybenzoic acid 8-(die thylamino)octyl ester (TMB-8), further suggesting that ANG II-dependen t sodium transport was mediated by inositol phosphates. Neither U-7312 2 nor TMB-8 prevented ANG II-dependent adenosine 3',5'-cyclic monophos phate (cAMP) decreases. Incubation with dibutyryl cAMP (10 mu M) or fo rskolin (10 mu M) prevented ANG II-dependent sodium flux as well as AN G II-dependent inositol phosphate formation. In conclusion, ANG II-dep endent proximal tubule sodium transport in cultured cells was transduc ed by phospholipase C and adenylyl cyclase. The adenylyl cyclase effec t on ANG II-dependent sodium transport was mediated by phospholipase C .