AJP - Cell Physiology, Vol 263, Issue 6 C1141-C1146, Copyright © 1992 by American Physiological Society
Modulation of Na-H exchange activity by angiotensin II in opossum kidney cells
M. Jourdain, C. Amiel and G. Friedlander
Department of Physiology, Faculte de Medecine Xavier-Bichat, Universite Paris, France.
Angiotensin II (ANG II) was shown to modulate transport in the renal
proximal tubule through both inhibition of adenylate cyclase and protein
kinase C (PKC) activation. We evaluated the effects of ANG II on adenosine
3',5'-cyclic monophosphate (cAMP) content and Na-H exchange activity
(amiloride-sensitive Na influx) in two strains of opossum kidney (OK) cells
originating from different sources, OK-VD and OK-RR cells. In OK-VD cells,
ANG II inhibited basal and parathyroid hormone (PTH)-induced cAMP
generation in a pertussis toxin-sensitive manner and reversed PTH
inhibition of Na-H exchange. These effects of ANG II were prevented by PD
123319, a selective nonpeptide antagonist of AT2 receptors. In contrast,
DuP 753, which antagonizes selectively AT1 receptors, had no effect. In
OK-RR cells, ANG II had no effect on cAMP content and decreased Na-H
exchange activity. The effect of ANG II persisted in the presence of PTH
but was abolished by PKC downregulation and by DuP 753, but not by PD
123319. In conclusion, two types of ANG II receptors, coupled to distinct
signaling pathways, were expressed independently in OK cells originating
from two different sources and mediated opposite effects of ANG II on Na-H
exchange activity. Those models provide a powerful tool for studying the
intracellular steps involved in the tubular effects of ANG II and to
evaluate the effect of pharmacological inhibitors of ANG II binding to its
receptors.
