Characterization of prostaglandin E receptor subtypes involved in the relaxation of rabbit penile corpus cavernosum smooth muscle

抄録

Prostaglandin E (PGE) induces the penile erection in the mammalians. Receptors for PGE were characterized to 4 different subtypes (EP1—4). The effects of agonists for EP1—4 receptors were studied on phenylephrine (PE, 1 μM)-induced contractions in the rabbit penile corpus cavernosum smooth muscle. The EP4 receptor agonist, ONO-AE1-329 (1 pM—10 μM), markedly relaxed the pre-contracted smooth muscle strips in a concentration-dependent fashion (−65 ± 16% relaxation at 10 nM). The EP2 receptor agonists, ONO-AE1-259-01 (1 nM—10 μM) or butaprost (1 nM—10 μM), also relaxed the smooth muscle strips in a concentration dependent fashion (−58 ± 10% relaxation at 10 μM or −53 ± 10% relaxation at 10 μM). The EP1 receptor agonist, ONO-DI-004 (0.01—10 μM), increased the contractility in the smooth muscle strips. A 12 ± 6% increase was observed with 10 μM of the agonist. The EP3 receptor agonist, ONO-AE-248 (0.01—10 μM), however, did not alter the contractility of the smooth muscle strips. The selective EP4 receptor antagonist, ONO-AE3-208 (0.1 μM), inhibited a relaxant response to ONO-AE1-329 (the EP4 receptor agonist) but did not affect a relaxant response to ONO-AE1-259-01 (the EP2 receptor agonist). It is likely that the relaxant effect of ONO-AE1-329 acts on the EP4 receptor. Neither a nitric oxide synthase (NOS) inhibitor, L-NAME (300 μM), nor a soluble guanylyl cyclase inhibitor, ODQ (30 μM), affected the relaxant responses to ONO-AE1-259-01 (0.1—10 μM) or ONO-AE1-329 (0.01 nM—1 μM). In summary, EP4 and/or EP2 receptors mediate relaxations in rabbit corpus cavernosum smooth muscle, and the EP4 relaxant system is higher in relaxant potency than the EP2 system. Furthermore, the relaxations are independent from a nitric oxide (NO)/cGMP signalling pathway.