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, nifedipine, 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⁺]_iobtained/[Ca²⁺]_ibasal 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.