Possible involvement of Ca2+-independent phospholipase A2 in protease-activated receptor-2-mediated contraction of rat urinary bladder.
Possible involvement of Ca(2+)-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 microM), an inhibitor of cyclooxygenase, or bromoenol lactone (BEL; 10 micro M), 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 microM), an inhibitor of cytosolic Ca(2+)-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.
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, 108-8641 Minato-ku, Tokyo, Japan.
Yuko
Y
Kubota
Tsutomu
T
Nakahara
Akiko
A
Mitani
Takeshi
T
Maruko
Maki
M
Saito
Kenji
K
Sakamoto
Kunio
K
Ishii
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D054522:Group VI Phospholipases A2; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology; D001743:Urinary Bladder / Q000201:enzymology* / Q000378:metabolism
D044464:Receptor, PAR-2; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; D054467:Phospholipases A2; D014357:Trypsin; D001920:Bradykinin