Angiotensin II directly increases rabbit renal brush-border membrane sodium transport: presence of local signal transduction system.
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(-7) M) was found to stimulate 22Na+ uptake by the isolated BBM vesicles directly. All did not affect the Na(+)-dependent BBM glucose uptake, and the effect of AII on BBM 22Na+ 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-beta S or PTX abolished, the effects of AII on BBM PLA and 22Na+ 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 BBM 22Na+ uptake, and activation of PLA by mellitin or addition of arachidonic acid similarly enhanced BBM 22Na+ uptake, suggesting the role of PLA activation in mediating AII's effect on BBM 22Na+ 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.
Morduchowicz
G A
GA
Division of Nephrology, Sepulveda Veterans Administration, California 91343.
Sheikh-Hamad
D
D
Dwyer
B E
BE
Stern
N
N
Jo
O D
OD
Yanagawa
N
N
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008555:Melitten / Q000494:pharmacology; D008871:Microvilli / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000493:pharmacokinetics*; D012979:Sodium Radioisotopes / Q000493:pharmacokinetics; D017923:Sodium-Hydrogen Exchangers
D001095:Arachidonic Acids; D002352:Carrier Proteins; D012979:Sodium Radioisotopes; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D008555:Melitten; D012964:Sodium; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins