Bradykinin induces a calcium-store- dependent calcium influx in mouse mesangial cells.
Bradykinin (BK) elicits extracellular-dependent [Ca2+](i) elevations in mouse mesangial cells (MMC) that are not blocked by verapamil, nifedipine, L-nicardipine, NiCl(2), or LaCl(3). 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 (IP(3), 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 IP(3)-sensitive store-dependent calcium influx in MMC. This phenomenon seems to involve tyrosine kinase and P-450 monooxygenase products in its transduction pathway.
Campos
Alexandre H
AH
Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Brazil.
Calixto
João B
JB
Schor
Nestor
N
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D004464:Econazole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D000925:Anticoagulants; D000935:Antifungal Agents; D001381:Azepines; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D009281:Naphthalenes; C070571:ML 7; D019284:Thapsigargin; D004464:Econazole; D006493:Heparin; D001920:Bradykinin; D002118:Calcium