Possible involvement of Ca²⁺-independent phospholipase A₂ in protease-activated receptor-2-mediated contraction of rat urinary bladder

Possible involvement of Ca²⁺-independent phospholipase A₂ (iPLA₂) was examined in protease-activated receptor-2 (PAR-2)-mediated contraction of the rat urinary bladder. Both PAR-2 activating peptide (PAR-2 AP; SLIGRL-NH₂) and trypsin produced a concentration-dependent contractile response in the urinary bladder preparations. These contractions were significantly (p<0.01) attenuated by indomethacin (10 μM), an inhibitor of cyclooxygenase, or bromoenol lactone (BEL; 10 μM), an inhibitor of iPLA₂. On the other hand, the contractile responses to bradykinin were not significantly affected by BEL, although they were reduced by indomethacin. Arachidonyltrifluoromethyl ketone (AACOCF₃; 30 μM), an inhibitor of cytosolic Ca²⁺-dependent phospholipase A₂, did not affect the trypsin- and bradykinin-induced contractions. Both indomethacin and BEL had no inhibitory effect on the prostaglandin E₂-induced contractions. These results suggest that PAR-2 activators and bradykinin stimulate the release of prostaglandins and thereby contract the rat urinary bladder smooth muscles. The release of prostaglandins by PAR-2 activators seems to be partly mediated by the iPLA₂.