REGULATION OF BRADYKININ RECEPTOR LEVEL BY CHOLERA-TOXIN, PERTUSSIS TOXIN AND FORSKOLIN IN CULTURED HUMAN FIBROBLASTS

1 The effect of bacterial toxins on bradykinin-triggered released of arachidonic acid was studied in serum-deprived human foreskin (HSWP) fibroblasts prelabelled with [H-3]-arachidonic acid. An 18-h exposure of HSWP cells to cholera toxin, pertussis toxin, or forskolin enhanced the bradykinin-stimulated release of arachidonic acid and metabolites. 2 Prolonged treatment of HSWP cells with these agents also caused a 3 to 4 fold rise in cell surface [H-3]-bradykinin binding. The rise was inhibited by concurrent incubation with cycloheximide or actinomycin D. In addition, cholera toxin and foreskolin increased [H-3]-bradykinin binding in wildtype PC12 cells, but not in mutant PC12 cells with reduced cyclic AMP-dependent protein kinase type II activity. 3 In conclusion, cholera toxin, pertussis toxin and forskolin enhanced arachidonic acid release in response to bradykinin, and increased the number of bradykinin receptors in HSWP fibroblasts. A cyclic AMP-dependent mechanism appears to mediate the actions of the toxins and forskolin.