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Bradykinin stimulates production of inositol (1,4,5) trisphosphate in cultured mesangial cells of the rat via a BK 2 ‐kinin receptor
Author(s) -
Bascands J.L.,
Emond C.,
Pecher C.,
Regoli D.,
Girolami J.P.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12284.x
Subject(s) - medicine , endocrinology , bradykinin , inositol phosphate , kinin , inositol trisphosphate , inositol , receptor , pertussis toxin , chemistry , egta , protein kinase c , mesangial cell , biology , g protein , calcium , signal transduction , biochemistry , kidney
1 Using [ 125 I‐Tyr 0 ]‐BK, as radiolabelled ligand, and various agonists and antagonists of bradykinin (BK) we identified a single class of specific BK 2 ‐binding sites in mesangial cell membranes ( B max = 73 fmol mg −1 protein and K d = 3.7 n m ). 2 Following the addition of 0.1 μ m BK, inositol (1,4,5) trisphosphate (IP3) formation increased within 20 s from a basal level of 64 to a maximal value of 175 pmol mg −1 protein. 3 Incubation in a Ca 2+ ‐free medium did not change IP3 production but a 5 min preincubation with 1 m m EGTA completely prevented the BK‐induced IP3 formation, suggesting that IP3 formation is partly dependent on extracellular calcium. 4 The BK 2 antagonist d ‐Arg‐Hyp 3 ‐ d ‐Phe 7 ‐BK (10 μ m ) but not the BK 1 antagonist (des‐Arg 9 ‐Leu 8 ‐BK) abolished IP3 production in response to 0.1 μ m BK. Pretreatment of mesangial cells with pertussis toxin was without effect on BK‐induced IP3 formation, whereas phorbol 12‐myristate 13‐acetate significantly enhanced (by 25%) BK‐induced IP3 formation. 5 The present data demonstrate that inositol phosphate breakdown in rat mesangial cells can be mediated via activation of a BK 2 ‐kinin receptor and is under negative control of protein‐kinase C.