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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. [ABSTRACT FROM AUTHOR]

We earlier reported that lidocaine augments the relaxation and accumulation of guanosine 3′,5′-cyclic monophosphate produced by atrial natriuretic peptide (ANP) in bovine tracheal smooth muscle contracted with methacholine. However, the mechanism of that augmentation remains to be elucidated. In this study, we examined the role of muscarinic receptor-mediated signalling in the potentiation of ANP-induced relaxation by lidocaine. Lidocaine (100 µM) augmented the relaxant responses to ANP in methacholine (0.3 µM)-contracted bovine tracheal smooth muscle but had no effect on the relaxant effects of ANP in preparations contracted with 100 µM histamine. Treatment of tracheal preparations with methoctramine (0.03 µM), an M2 muscarinic receptor antagonist, enhanced ANP-induced relaxation and this treatment abolished the synergistic action of lidocaine on ANP. In radioligand-binding experiments, lidocaine concentration dependently displaced the specific binding of [3H]-N-methyl scopolamine to cloned human M2 and M3 muscarinic receptors expressed in Chinese hamster ovary cells. These results suggest that lidocaine acts as an M2 muscarinic receptor antagonist, thereby potentiating the relaxant responses to ANP in the bovine tracheal smooth muscle contracted with muscarinic receptor agonists. [ABSTRACT FROM AUTHOR]

The influence of muscarinic M2 receptors to modulate the relaxant effects of atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP) was investigated in bovine tracheal smooth muscle. In bovine tracheal smooth muscles contracted with methacholine (0.3 µM), methoctramine (0.03 µM), a selective muscarinic M2 receptor antagonist, augmented the relaxant responses to ANP without affecting the responses to SNP and 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate. Pertussis toxin (PTX; 200 ng/ml for 18 h) augmented the relaxation and accumulation of guanosine 3',5'-cyclic monophosphate produced by ANP. These results suggest that the stimulation of muscarinic M2 receptors suppresses ANP-induced activation of particulate guanylyl cyclase via a PTX-sensitive G protein. [ABSTRACT FROM AUTHOR]

We examined how diabetes affects the β-adrenoceptor subtypes mediating relaxation of rat urinary bladder smooth muscle contracted with carbachol. The relaxant responses to isoproterenol were larger in muscles from rats 8 to 10 weeks after induction of diabetes with streptozotocin (80 mg/kg, i.p.) as compared to the control muscles. In contrast, forskolin-induced relaxations did not differ significantly in the control and diabetes groups. Propranolol (1 μM) abolished the diabetes-induced augmentation of relaxant responses to isoproterenol. The relaxant responses to T-0509 ((−)-(R)-1-(3,4-dihydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)-amino]ethanol hydrochloride), a β1-adrenoceptor agonist, were small but significantly augmented by diabetes. On the other hand, diabetes did not change the relaxations produced by clenbuterol, a β2-adrenoceptor agonist, and BRL37344 ((±)-(R*,R*)-(4-[2-([2-(3-chlorophenyl)-2-hydroxyethyl]amino)propyl]phenoxy)acetic acid), a β3-adrenoceptor agonist. These results suggest that diabetes selectively augments the β1-adrenoceptor-mediated relaxation of the rat urinary bladder smooth muscle. [Copyright &y& Elsevier]