Effects of kinins upon cytosolic calcium concentrations in mouse mesangial cells

Effects of kinins upon cytosolic calcium concentrations in mouse mesangial cells

Author Campos, A. H. Google Scholar
Calixto, J. B. Google Scholar
Schor, N. Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Federal de Santa Catarina (UFSC)
Abstract Bradykinin (BK) induces increases in cytosolic calcium concentration [Ca++](i) in several cell lines. Because the role of BK in the renal system, particularly in mesangial cell (MC), is not clear, we investigated the effects of kinins on [Ca++](i) in mouse-immortalized MC. [Ca++](i) was evaluated by spectrofluorometry and expressed as a ratio between the obtained and basal [Ca++](i). BK (0.1 mu M) induced a non-sustained increase in [Ca++](i) (4.70 +/- 0.27; N = 28). A similar effect was observed with the B-2 receptor agonist, Tyr(8)-BK (0.1 mu M, 3.34 +/- 0.48; N = 7), while B-1 receptor agonists, des-Arg(10)-Kal-lidin (Kal) (1 mu M, N = 11) and des-Arg(9)-BK (1 mu M, N = 8), exhibited only discrete responses (1.45 +/- 0.08 and 1.12 +/- 0.04, respectively). Cross-desensitization was seen between BK and Tyr(8)-BK, but not between BK and des-Arg(10)-Kal. the BK response was decreased (5.09 +/- 0.30, N = 6 to 1.57 +/- 0.12, N = 7, P < 0.001) by the B-2 receptor antagonist HOE 140 (0.1 mu M, 15 min), while the B-1 receptor antagonist des-Arg(9)-[Leu(8)]-BK (1 mu M, 15 min) had no effect on BK or des-Arg(10)-Kal actions. Incubation of cells with Escherichia coli lipopolysaccharide (100 mu g/ml, 24 h) alone or in association with tumor necrosis factor-alpha (TNF-alpha) (10 ng/ml, N = 6) did not enhance B-1 agonist responses. BK was inhibited by repeated cell washouts in zero Ca++ solution (2.04 +/- 0.19, N = 6 r < 0.001), and the residual response was almost abolished by thapsigargin (Thaps) a sarcoplasmic reticulum (SR) calcium-ATPase inhibitor (1 mu M) (1.18 +/- 0.08, N = 5 P < 0.001). Additionally, BK was not inhibited by verapamil (50 mu M), nifedipine (30 mu M), Ni++ (300 mu M) or La+++ (10 mu M). in conclusion, BK induces [Ca++](i) in mouse MC mainly by B-2 receptor activation. B-1 receptors have a minor role in this phenomenon even in the presence of known B1 receptor synthesis inducers. Finally, BK mobilizes extracellular calcium sources and, to a lesser extent, intracellular Thaps-sensitive calcium stores. the ion channels involved in calcium influx remain to be detected. (C) 1999 Elsevier Science B.W. All rights reserved.
Keywords mesangial cell
bradykinin
cytosolic calcium
bradykinin receptors
Language English
Date 1999-12-01
Published in Immunopharmacology. Amsterdam: Elsevier Science Bv., v. 45, n. 1-3, p. 39-49, 1999.
ISSN 0162-3109 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 39-49
Origin http://dx.doi.org/10.1016/S0162-3109(99)00056-9
Access rights Closed access
Type Article
Web of Science ID WOS:000084080100008
URI http://repositorio.unifesp.br/handle/11600/26185

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