Prejunctional inhibitory effects of isoprostanes on dopaminergic neurotransmission in bovine retinae, in vitro.
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.
Department of Ophthalmology, Sichuan Provincial People Hospital, Chengdu, Sichuan 610072, PR China.
Hong
H
Liu
Min
M
Zhao
Catherine A
CA
Opere
D000818:Animals; D002417:Cattle; D004298:Dopamine / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects*; D066298:In Vitro Techniques; D028421:Isoprostanes / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
D028421:Isoprostanes; D011188:Potassium; D004298:Dopamine