DIRECT ACTION OF BRL-38227 AND GLIBENCLAMIDE ON INTRACELLULAR CALCIUM STORES IN CULTURED AIRWAY SMOOTH-MUSCLE OF RABBIT

The effects of BRL 38227 and glibenclamide on intracellular calcium stores were investigated in permeabilized cultured airway smooth muscle cells of the rabbit using Ca-45 effluxes. BRL 38227 (10-mu-M) reduced loading of the inositol 1,4,5-trisphosphate (InsP3)-sensitive intracellular store by 26.5% +/- 1.0; this effect was antagonized by 1-mu-M glibenclamide. BRL 38227 itself did not release calcium and had no effect on guanosine 5'-0-(3-thiotriphosphate)-induced calcium release. Glibenclamide (greater-than-or-equal-to 5-mu-M) also reduced calcium loading of the intracellular store, and enhanced calcium release. These results suggest that BRL 38227 has a direct effect on intracellular calcium handling.