Prejunctional Inhibitory Effects of Isoprostanes on Dopaminergic Neurotransmission in Bovine Retinae, In vitro

Abstract

We investigated the effect of isoprostanes (IsoPs) on potassium (K+)-depolarization-evoked release of [3H]dopamine from isolated bovine retinae. Isolated retinae were preloaded with [3H]dopamine and then prepared for studies of [3H]dopamine release using the superfusion method. 8-iso(15R)PGF 2alpha, 8-isoPGE2, 8-isoPGE1 and 8-isoPGF 2alpha attenuated [3H]dopamine release from isolated bovine retinae. At a concentration of 1 microM, the rank order of activity displayed by IsoP agonists was: 8-iso(15R)PGF 2alpha > 8-isoPGE2 > 8-isoPGE1 > 8-isoPGF 2alpha. Inhibition of cyclooxygenase (COX) with flurbiprofen reversed the effects caused by 8-isoPGE2 (10 nM and 10 microM), 8-iso(15R)PGF 2alpha (1 microM) and 8-isoPGE1 (1 microM). Although the EP1/EP2 antagonist, AH 6809 (10 microM) had no significant effect on K+-induced [3H]dopamine release, it blocked the inhibitory effect of both 8-isoPGE1 (10 microM) and 8-isoPGE2 (10 microM). In conclusion, IsoPs attenuate K+-induced [3H]dopamine release in isolated bovine retinae, presumably via an indirect action on COX pathway leading to the production of prostanoids, which in turn, activates EP receptors.