Dopamine inhibits melatonin release in the mammalian retina: in vitro evidence

A circadian oscillator located within the retina controls melatonin synthes is in the retina of mammals. In non-mammalian vertebrates retinal melatonin and dopamine appear to act as mutually inhibitory paracrine signals for ni ght and day, respectively; while in mammals this mutually inhibitory capabi lity has now been fully demonstrated. In this study using a flow-through cu lture apparatus we investigated melatonin release from cultured retinas of golden hamster (Mesocricetus auratus) in the presence of dopamine or dopami nergic agonists and antagonists. Neural retinas were cultured with medium 1 99 for 24 h in a flow-through apparatus at the temperature 33 degrees C, Du ring the subjective night the culturing medium was supplemented with dopami ne, dopamine receptor antagonists or agonists. At the concentration of 0.1 mu M dopamine did not inhibit melatonin release, while at higher dopamine c oncentration (1 to 1000 mu M) melatonin release was inhibited in a dose-dep endant manner. These effects appeared to be mediated by a D-2/D-4 receptor, because D-2 and D-4 receptor agonists (100 mu M), but not D-1/D-5 receptor agonists (100 mu M), inhibited melatonin release. Furthermore, D-2/D-4 sel ective receptor antagonists (100 mu M) in conjunction with 100 mu M dopamin e blocked melatonin suppression, whereas a D-1/D-5 selective receptors anta gonist was completely ineffective. Taken together, these results directly d emonstrate for the first time that in the retina of mammals dopamine may su ppress melatonin, and that suppression is mediated by D-2/D-4 dopaminergic receptors. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights r eserved.