ANGIOTENSIN II-DEPENDENT PROXIMAL TUBULE SODIUM-TRANSPORT REQUIRES RECEPTOR-MEDIATED ENDOCYTOSIS

Angiotensin II (ANG II) receptors are present on apical and basolatera l surfaces of proximal tubule cells. To determine the cellular mechani sms of proximal tubule ANG II receptor-mediated Na transport, apical-t o-basolateral Na-22 flux was measured in cultured proximal tubule cell s. Apical ANG II caused increases in Na-22 flux (maximum response: 100 nM, 30 min). Basolateral ANG II resulted in Na-22 flux that was 23-56 % greater than Na-22 flux observed with equimolar apical ANG II. Apica l ANG II-induced Na-22 flux was prevented by preincubation with amilor ide, ouabain, and the AT(1) receptor antagonist losartan. Because apic al ANG II signaling was previously shown to be endocytosis dependent, we questioned whether endocytosis was required for ANG II-stimulated p roximal tubule Na transport as well. Apical (but not basolateral) ANG II-dependent Na-22 flux was inhibited by phenylarsine oxide, an agent which prevents ANG II receptor internalization. In conclusion, apical and basolateral ANG II caused proximal tubule Na transport. Apical ANG II-dependent Na flux was mediated by AT(1) receptors, transcellular t ransport pathways, and receptor-mediated endocytosis.