BRADYKININ STIMULATES THE INTRACELLULAR CALCIUM ACTIVITY IN HUMAN MESOTHELIAL CELLS

Aim. The aim of this study was to investigate the influence of bradyki nin on the intracellular calcium activity ([Ca2+](i)) in human mesothe lial cells in culture. Results. Bradykinin (1-1000 nmol/l) caused a co ncentration-dependent and reversible increase of [Ca2+](i) in mesothel ial cells (n=94); 10 nmol/l bradykinin increased [Ca2+](i) from 23 +/- 9 to 670 +/- 170 nmol/l (n = 36). The pattern of the bradykinin-induc ed [Ca2+](i) increase was biphasic with a transient [Ca2+](i) peak, wh ich was followed by a sustained [Ca2+](i) plateau. The bradykinin-medi ated [Ca2+](i) plateau, but not the peak, was inhibited in a solution with an extracellular reduced Ca2+ concentration (from 1000 to 1 mu mo l/l, n=11). Flufenamate (greater than or equal to 10 mu mol/l), an inh ibitor of non-selective ion channels abolished the bradykinin-mediated increase of [Ca2+](i), whereas the L-type Ca2+ channel blocker nicard ipine (10 mu mol/l) had no effect (n=3-5). The [Ca2+](i) response to b radykinin was inhibited by the BK, antagonist Hoe 140 (IC50 +/- k7 nmo l/l, n = 30). Conclusions. The data indicate that bradykinin stimulate s [Ca2+](i) in mesothelial cells by a release of Ca2+ from intracellul ar stores and an influx from Ca2+ through non-selective channels via a BK2 receptor.