Bradykinin induces a calcium-store-dependent calcium influx in mouse mesangial cells

Abstract

Bradykinin (BK) elicits extracellular-dependent [Ca2+]i elevations in mouse mesangial cells (MMC) that are not blocked by verapamil, nifeclipine, L-nicardipine, NiCl2, or LaCl3. the aim of the present study was to evaluate the mechanisms involved in calcium influx induced by BK in MMC. [Ca2+](i) was analyzed through spectrofluorometry employing fura-2-AM, and the data were expressed as [Ca2+](i) obtained/[Ca2+](i) basal ratio. Heparin (IP3, a receptor antagonist) almost abolished the effects of BK in MMC (1.85 +/- 0.15 vs. 1.13 +/- 0.02, n = 4, p = 0.001). Following external and intracellular calcium store depletion, BK's effect was absent even after successful extracellular calcium replenishment. ML-7 (a myosin light chain kinase inhibitor) blocked responses to thapsigargin (2.62 +/- 0.13 vs. 1.11 +/- 0.04, n = 4, p < 0.001), but not those of BK (6.51 +/- 0.39, n = 6, vs. 5.86 +/- 1.17, n = 4, p = 0.39). On the other hand, genistein (a tyrosine kinase inhibitor) was able to inhibit thapsigargin (3.12 +/- 0.22, n = 5, vs. 1.28 +/- 0.16, n = 4, p < 0.001) as well as BK responses (6.46 +/- 0.66 vs. 2.89 +/- 0.61, n = 4, p < 0.05). Econazole (a P-450 monooxygenase inhibitor) inhibited the responses to both thapsigargin (3.45 +/- 0.16 vs. 1.03 +/- 0.03, n = 4, p < 0.001) and BK (6.49 +/- 0.83, n = 6, vs. 1.17 +/- 0.08, n = 4, p = 0.01). Finally, responses to BK were not affected by indomethacin (6.69 +/- 0.66 vs. 6.57 +/- 0.87, n = 4, p = 0.916). Thus, BK promotes an IP3-sensitive store-dependent calcium influx in MMC. This phenomenon seems to involve tyrosine kinase and P-450 monooxygenase products in its transduction pathway. Copyright (C) 2002 S. KargerAG, Basel.Universidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, BrazilUniv Fed Santa Catarina, Ctr Biol Sci, Div Pharmacol, Florianopolis, SC, BrazilUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, BrazilWeb of Scienc