Ohia S E, Opere C, Tang L, al-Zadjali K
Department of Pharmaceutical Sciences and Pharmacology, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, Nebraska, USA.
J Ocul Pharmacol Ther. 1995 Spring;11(1):73-81. doi: 10.1089/jop.1995.11.73.
Exogenous prostaglandins (PGs) have been shown to inhibit dopamine (DA) release from the rabbit retina via an effect on presynaptic EP3-receptors. In the present study, we investigated the possible involvement of cyclic AMP in DA release and in the prostanoid receptor mediated regulation of DA release from the neural retina. Both forskolin and 8-bromo-cyclic AMP enhanced field stimulation-evoked [3H]DA release from isolated, superfused rabbit retinas without affecting basal tracer efflux suggesting that presynaptic cyclic AMP may be involved in the pathway leading to DA release. Forskolin attenuated inhibition of evoked [3H]DA release caused by low but not high concentrations of PGE2. Both PGE2 and sulprostone had no significant effect on basal cyclic AMP levels but inhibited forskolin-stimulated cyclic AMP formation. Furthermore, sulprostone was more potent than PGE2 in attenuating forskolin-activated cyclic AMP production. The inhibition of forskolin-elevated cyclic AMP levels caused by PGE2 was, however, unaffected by the EP1-receptor antagonist, AH6809. We conclude that the regulation of DA release by presynaptic prostanoid EP3-receptors may be mediated, at least in part, through an inhibitory effect on adenylyl cyclase.
外源性前列腺素（PGs）已被证明可通过对突触前EP3受体的作用抑制兔视网膜中多巴胺（DA）的释放。在本研究中，我们研究了环磷酸腺苷（cAMP）在DA释放以及前列腺素受体介导的神经视网膜DA释放调节中的可能作用。福斯高林和8-溴环磷酸腺苷均增强了离体、灌注兔视网膜的场刺激诱发的[3H]DA释放，而不影响基础示踪剂流出，这表明突触前cAMP可能参与了导致DA释放的途径。福斯高林减弱了低浓度但非高浓度前列腺素E2（PGE2）对诱发的[3H]DA释放的抑制作用。PGE2和舒前列素对基础cAMP水平均无显著影响，但抑制了福斯高林刺激的cAMP形成。此外，舒前列素在减弱福斯高林激活的cAMP产生方面比PGE2更有效。然而，PGE2对福斯高林升高的cAMP水平的抑制作用不受EP1受体拮抗剂AH6809的影响。我们得出结论，突触前前列腺素EP3受体对DA释放的调节可能至少部分是通过对腺苷酸环化酶的抑制作用介导的。
