Role of prostanoids in the contraction induced by a tachykinin NK2 receptor agonist in the hamster urinary bladder

In isolated strips of the hamster urinary bladder the selective tachykinin NK2 receptor agonist [beta Ala(8)]NKA(4-10) induced a concentration-depende nt (1 nM-10 mu M) contraction (EC50 104 nM) associated significant release of prostaglandin E-2 (PGE(2), 50+/-17 pg/mg tissue). In mucosa-free bladder strips [beta Ala(8)]NKA(4-10) was as potent as in the presence of mucosa ( EC50 46 nM), although the evoked PGE(2) release was significantly less than in controls (6+/-1.7 pg/mg tissue). Dexketoprofen (10 mu M) produced a sig nificant but limited rightward shift of the concentration/response curve to [beta Ala(8)]NKA(3-10) both in the presence and absence of the mucosal lay er: the EC50 for [beta Ala(8)]NKA(4-10) was increased five- and threefold, respectively, The evoked PGE(2) release was abolished in both cases. The se lective tachykinin NK2 receptor antagonist, nepadutant (10 nM-1 mu M) produ ced a concentration-dependent and even inhibition of both contraction and P GE(2) release induced by [beta Ala(8)]NKA(4-10). The L-type calcium channel blocker, nifedipine (1 mu M) and the non-selective cationic channel blocke r SKF 96365 (30 mu M) both inhibited the contractile response to [beta Ala( 8)]NKA(4-10) (89+/-2 and 83+/-2% inhibition, respectively). The evoked PGE( 2) release was not affected by nifedipine but was almost abolished by SKF 9 6365, Arachidonic acid (100 mu M) induced a contractile response (5.9+/-0.7 mN) associated with a large production of PGE(2) (383+/-78 pg/mg tissue). The contractile response to arachidonic acid was inhibited by both nifedipi ne (1 mu M) and SKF 96365 (30 mu M) (83+/-5 and 79+/-3% inhibition, respect ively). The PGE(2) production induced by arachidonic acid was markedly inhi bited by SKF 95365 only (about 94% inhibition). Exogenous PGE(2) contracted hamster bladder strips in the presence of dexketoprofen (EC50 1 mu M) and strongly potentiated the contractile response to a submaximal concentration of [beta Ala(8)]NKA(4-10). In anaesthetized hamsters the administration of [beta Ala(8)]NKA(4-10) (10 nmol/kg, i.v.) produced a contractile response of the urinary bladder (13+/ -0.3 mm Hg) that was inhibited partly by dexketoprofen (25+/-3 and 35+/-4% inhibition for 0.2 and 2 mg/kg, i.v. dexketoprofen, respectively). We conclude that activation of tachykinin NK2 receptors determines prostano id synthesis/release in the hamster urinary bladder and that this effect is largely ascribable to structures present in the bladder mucosa. Prostanoid s generated following NK2 receptor activation amplify the direct contractil e effect of NK2 receptor agonists. This latter response is largely due to a ctivation of L-type calcium channels (nifedipine-sensitive) although this s ource of calcium apparently is not essential for activation of prostanoid s ynthesis.