Dopamine is a major catecholamine in vertebrate retina. The amine is localized, depending on the species, in a subset of amacrine and/or interplexiform cells. The dopamine-containing cells in retina are activated upon light exposure, with resulting increase in the amine synthesis and release. Dopamine, acting as a light-adaptive signal, controls many aspects of retinal physiology; among its diverse effects is modulation of the night-driven melatonin biosynthesis, which occurs in photoreceptors. Activation of dopamine receptors belonging to D2-family, localized on photoreceptors, rapidly suppresses the nocturnal cyclic AMP-dependent activity of serotonin N-acetyltransferase (NAT), a key regulatory enzyme in melatonin biosynthesis. Convincing evidence indicates that these NAT activity-modulating receptors represent the D4-subtype dopamine receptors, which--most probably indirectly--control in a negative manner the activity of intraphotoreceptor Ca2+/calmodulin-dependent adenylyl cyclase. This article reviews current knowledge on dopamine D4-subtype receptors, with a special emphasis to their function in vertebrate retina. In addition, some findings resulting from our recent experiments with newly synthesized D4-receptor-selective ligands are presented and discussed. It is proposed that the avian retina, with its ability to synthesize melatonin in a dopamine-sensitive manner (via D4-like dopamine receptor), may offer a suitable specific in vivo model which allows to study potential ligands (both agonists and antagonists) of the D4-subtype dopamine receptor.
