Dopamine inhibits melatonin synthesis in photoreceptor cells through a D2-like receptor subtype in the rat retina: biochemical and histochemical evidence.

An intrinsic oscillator, using dopamine and melatonin as antagonist signals, controls rhythmic events in the retina of nonmammals. The purpose of the present work was to localize and characterize a dopamine receptor responsible for the nocturnal inhibition of melatonin synthesis in photoreceptor cells in a mammalian retina. An antibody against the D-2 receptor stained photoreceptor cell inner segments of the rat retina. alpha-Methyl-p-tyrosine, a competitive inhibitor of tyrosine hydroxylase, enhanced the nocturnal content of melatonin, suggesting the dopamine control of melatonin synthesis as in nonmammals. Clozapine, a D-2C/D-4 antagonist, also enhanced the nocturnal level of melatonin, whereas raclopride, a D-2A antagonist, did not. Taken together, these results support the control of melatonin levels by dopamine through a D-2C/D-4 receptor in photoreceptor cells of the rat retina, The presence of D-4 receptors in the rat retina was confirmed by reverse transcription-PCR.