Dopamine D4-like receptors in vertebrate retina: does the retina offer a model for the D4-receptor analysis?

Aug 1, 1997Polish journal of pharmacology

Dopamine D4-like receptors in the vertebrate retina: can the retina serve as a model to study D4 receptors?

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Abstract

Dopamine is implicated in regulating melatonin biosynthesis in the vertebrate retina.

Dopamine is found in specific cells of the retina, which vary by species.
Light exposure activates dopamine synthesis and release in retinal cells.
Dopamine modulates various retinal functions, including the production of melatonin.
D2-family dopamine receptors on photoreceptors inhibit an enzyme critical for melatonin synthesis.
Evidence suggests that the D4-subtype of dopamine receptors plays a key role in this regulatory mechanism.
Recent experiments indicate that the avian retina may serve as a model for studying D4-receptor ligands.

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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.

Dopamine D4-like receptors in vertebrate retina: does the retina offer a model for the D4-receptor analysis?

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