Dopamine D4-like receptors in vertebrate retina: does the retina offer a model for the D4-receptor analysis?
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.
Zawilska
J B
JB
Department of Biogenic Amines, Polish Academy of Sciences, Lódź, Poland.
Nowak
J Z
JZ
D000595:Amino Acid Sequence; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D002645:Chickens; D002940:Circadian Rhythm; D000242:Cyclic AMP / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008027:Light; D008550:Melatonin / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010786:Photoreceptor Cells / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D012160:Retina / Q000378:metabolism*
C493593:DRD3 protein, human; C493599:DRD4 protein, human; C493605:DRD5 protein, human; D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin; D004298:Dopamine