Angiotensin II directly increases rabbit renal brush-border membrane sodium transport: Presence of local signal transduction system |
| |
Authors: | Gabriel A. Morduchowicz David Sheikh-Hamad Barney E. Dwyer Naftali Stern Oak D. Jo Norimoto Yanagawa |
| |
Affiliation: | (1) Division of Nephrology, Neurology Medical and Research Services, Sepulveda Veterans Administration Medical Center, 91343 Sepulveda, California;(2) Division of Endocrinology, Medical and Research Services, Sepulveda Veterans Administration Medical Center, 91343 Sepulveda, California;(3) Department of Medicine, University of California at Los Angeles, School of Medicine, Los Angeles, California |
| |
Abstract: | Summary In the present study, we have examined the direct actions of angiotensin II (AII) in rabbit renal brush border membrane (BBM) where binding sites for AII exist. Addition of AII (10–11–10–7m) was found to stimulate22Na– uptake by the isolated BBM vesicles directly. AII did not affect the Na+-dependent BBM glucose uptake, and the effect of AII on BBM22Na+ uptake was inhibited by amiloride, suggesting the involvement of Na+/H+ exchange mechanism. BBM proton permeability as assessed by acridine orange quenching was not affected by AII, indicating the direct effect of AII on Na+/H+ antiport system.In search of the signal transduction mechanism, it was found that AII activated BBM phospholipase A2 (PLA) and that BBM contains a 42-kDa guanine nucleotide-binding regulatory protein (G-protein) that underwent pertussis toxin (PTX)-catalyzed ADP-ribosylation. Addition of GTP potentiated, while GDP-ßS or PTX abolished, the effects of AII on BBM PLA and22Na+ uptake, suggesting the involvement of G-protein in AII's actions. On the other hand, inhibition of PLA by mepacrine prevented AII's effect on BBM22Na+ uptake, and activation of PLA by mellitin or addition of arachidonic acid similarly enhanced BBM22Na+ uptake, suggesting the role of PLA activation in mediating AII's effect on BBM22Na+ uptake.In summary, results of the present study show a direct stimulatory effect of AII on BBM Na+/H+ antiport system, and suggest the presence of a local signal transduction system involving G-protein mediated PLA activation. |
| |
Keywords: | angiotensin II renal brush border membrane Na+/H+ exchange phospholipase A2 GTP-binding protein |
本文献已被 SpringerLink 等数据库收录! |
|