title: Angiotensin II directly increases rabbit renal brush-border membrane sodium transport: presence of local signal transduction system.
abstract: 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.
authors.affiliation: Division of Nephrology, Sepulveda Veterans Administration, California 91343.
authors.forename: G A
authors.initials: GA
authors.lastname: Morduchowicz
authors.forename: D
authors.initials: D
authors.lastname: Sheikh-Hamad
authors.forename: B E
authors.initials: BE
authors.lastname: Dwyer
authors.forename: N
authors.initials: N
authors.lastname: Stern
authors.forename: O D
authors.initials: OD
authors.lastname: Jo
authors.forename: N
authors.initials: N
authors.lastname: Yanagawa
mesh_terms: 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
chemical_list: 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