Angiotensin II and proximal tubule sodium transport.
As a target site for angiotensin II (A-II), renal proximal tubule is unique in that it may be equipped with a local A-II generating system and that both basolateral and apical membranes may be accessible for A-II's action. We have recently conducted studies to examine these possibilities. With in vitro cultured proximal tubular cells, we have demonstrated de novo synthesis of angiotensinogen and renin. With isolated renal brush border membrane (BBM), we have confirmed the presence of A-II receptors and found that A-II directly stimulated BBM Na(+)-H+ exchange. In search of the signal transduction mechanism, we have found that A-II also activated BBM phospholipase A2 (PLA) and that BBM contained a pertussis toxin-sensitive guanine nucleotide binding protein (G-protein) which mediates the effects of A-II. Further studies showed that prevention of PLA activation abolished A-II's effect on Na(+)-H+ exchange, and that activation of PLA by mellitin and addition of arachidonic acid similarly enhanced Na(+)-H+ exchange activity, suggesting that PLA activation may mediate the stimulatory effect of A-II on Na(+)-H+ exchange. These results thus indicate that a local signal transduction mechanism involving G-protein mediated PLA activation exists in renal BBM which mediates A-II's effect on Na(+)-H+ exchange. Taken together, we propose that, independent of A-II in the circulation, local luminal A-II may serve as an important regulatory system on sodium transport in renal proximal tubule.
Yanagawa
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Nephrology Division, Sepulveda Veterans Administration Medical Center, Calif.
D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001693:Biological Transport, Active; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D000804:Angiotensin II; D012964:Sodium; D012083:Renin