B2 receptor-mediated dual effect of bradykinin on proximal tubule Na+ -ATPase: sequential activation of the phosphoinositide-specific phospholipase Cbeta/protein kinase C and Ca2+ -independent phospholipase A2 pathways.
In a previous paper we showed that bradykinin (BK), interacting with its B2 receptor, inhibits proximal tubule Na+ -ATPase activity but does not change (Na+ +K+)ATPase activity. The aim of this paper was to investigate the molecular mechanisms involved in B2-mediated modulation of proximal tubule Na+ -ATPase by BK. To abolish B1 receptor-mediated effects, all experiments were carried out in the presence of (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Leu), des-Arg9-[Leu8]-BK (DALBK), a specific antagonist of B1 receptor. A dual effect on the Na+ -ATPase activity through the B2 receptor was found: short incubation times (1-10 min) stimulate the enzyme activity; long incubation times (10-60 min) inhibit it. The stimulatory effect of BK is mediated by activation of phosphoinositide-specific phospholipase C beta (PI-PLCbeta)/protein kinase C (PKC); its inhibitory action is mediated by Ca2+ -independent phospholipase A2 (iPLA2). Prior activation of the PI-PLCbeta/PKC pathway is required to activate the iPLA2-mediated inhibitory phase. These results reveal a new mechanism by which BK can modulate renal sodium excretion: coupling between B2 receptor and activation of membrane-associated iPLA2.
Líbano-Soares
J D
JD
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Gomes-Quintana
E
E
Melo
H K
HK
Queiroz-Madeira
E P
EP
Roubach
R G
RG
Lopes
A G
AG
Caruso-Neves
C
C
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D043782:Receptor, Bradykinin B2 / Q000502:physiology*
D027682:Cation Transport Proteins; D043782:Receptor, Bradykinin B2; D011493:Protein Kinase C; D054467:Phospholipases A2; D054801:Phosphoinositide Phospholipase C; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D001920:Bradykinin; D002118:Calcium