INHIBITORY EFFECT OF PROSTAGLANDINS ON DOPAMINE RELEASE FROM THE RETINA

1. Prostaglandins have been shown to modulate transmitter release from both central and peripheral neuroeffector junctions. In the present s tudy, we examined the effect of prostaglandins on [H-3]-dopamine relea se from isolated, superfused rabbit retina. 2. Both naturally occurrin g and synthetic prostaglandins produced concentration-dependent reduct ion of electrically evoked [H-3]-dopamine overflow without affecting b asal tracer efflux. The rank order of potencies of the agonists was: s ulprostone > 16,16-dimethyl PGE2 > PGE2 > > 11-deoxy-PGE1 > PGF2x. 3. The PGE2-mediated inhibition of field stimulated [H-3]-dopamine releas e was not blocked by the selective EP1-receptor antagonist, AH6809 (5- 30 muM). 4. The cyclooxygenase inhibitor, flurbiprofen (3 muM) had no effect on basal or evoked [H-3]-dopamine overflow nor did it affect th e inhibition caused by PGE2 suggesting that endogenous prostaglandins are not involved in the regulation of dopamine release in the retina. 5. The inhibition of [H-3]-dopamine release produced by submaximal con centrations of PGE2, apomorphine and melatonin were not additive indic ating that presynaptic PGE2, D2- and melatonin receptors coexist at si tes for neurotransmitter release and may share a common mechanism for regulation of dopamine release.6. We conclude that prostaglandin-induc ed inhibition of electrically evoked [H-3]-dopamine release from the r abbit retina may be mediated by specific prostaglandin receptors of th e EP3 subtype.