PLA2/PGE2 are involved in the inhibitory effect of bradykinin on the angiotensin-(1-7)-stimulated Na(+)-ATPase activity of the proximal tubule.
Recently, we demonstrated that bradykinin (BK) counteracts the stimulatory effect of Ang-(1-7) on the Na(+)-ATPase activity from basolateral membrane of the proximal tubule through B2 receptor. In the present paper, the signaling pathway involved in the inhibitory response of the Na(+)-ATPase activity to BK was investigated. The following results indicate that the phospholipase A2 (PLA2)/COX/prostaglandin E (PGE2) pathway is implicated in this process: (1) The inhibitory effect of BK on Ang-(1-7)-stimulated enzyme is abolished in a dose-dependent manner by quinacrine (10(-9)-10(-6)M), a nonspecific PLA2 inhibitor, and by PACOCF3 (10(-7)M), an inhibitor of a Ca(2+)-independent PLA2. However, AACOCF3 (2 x 10(-4) M), an inhibitor of the cytosolic PLA2, does not modify the inhibitory effect of BK. (2) The inhibitory effect of BK on the Ang-(1-7)-stimulated enzyme is reversed by cyclooxygenase (COX) inhibitors diclofenac (10(-12) M) and indomethacin (10(-12) M). (3) PGE2 (10(-12)-10(-5) M) inhibits the Na(+)-ATPase activity in a dose dependent manner. (4)The inhibitory effects of PGE2 and BK on the Na(+)-ATPase activity are not cumulative. (5) PGE2 (10(-12)-10(-8) M) counteracts the stimulatory effect of Ang-(1-7) on the enzyme activity in a dose-dependent manner.
Lopes
A G
AG
Instituto de Biofísica Carlos Chagas, Universidade Federal do Rio de Janeiro, CCS-Bloco G, Rio de Janeiro RJ, 21949-900 Brazil.
Soares
A C
AC
Santos
D P A
DP
Fernandes
M S
MS
Leão-Ferreira
L R
LR
Quintana-Gomes
E
E
Caruso-Neves
C
C
D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D065094:Bradykinin B2 Receptor Antagonists; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D004008:Diclofenac / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
D065094:Bradykinin B2 Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D010446:Peptide Fragments; D043782:Receptor, Bradykinin B2; D004008:Diclofenac; D000803:Angiotensin I; D010741:Phospholipases A; D054467:Phospholipases A2; D000254:Sodium-Potassium-Exchanging ATPase; D011796:Quinacrine; C118790:angiotensin I (1-7); D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin