Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

J Neurosci. 1995 Mar;15(3 Pt 2):2179-85. doi: 10.1523/JNEUROSCI.15-03-02179.1995.


The possible interaction of melatonin receptors and D1 dopamine receptors was investigated in neural cells prepared from embryonic day 8 chick retinas and cultured for 6 d. Dopamine stimulated cAMP accumulation in cultured retinal cells. This effect of dopamine was antagonized by addition of dopamine receptor antagonists (haloperidol and SCH23390) or melatonin receptor agonists (melatonin, 2-iodomelatonin, and 6-chloromelatonin). The inhibition of dopamine-stimulated cAMP accumulation by melatonin was concentration dependent, with half-maximal inhibition at approximately 160 pM. Melatonin inhibited the effect of dopamine at all dopamine concentrations, suppressing the maximal response to the neurotransmitter by approximately 70%. Melatonin also inhibited the stimulation of cAMP accumulation by SKF 82958, a selective D1 dopamine receptor agonist. Pretreatment of cultures with pertussis toxin had no significant effect on dopamine-stimulated cAMP accumulation, but inhibited the response to melatonin. In contrast to its effect on cAMP accumulation, melatonin had no effect on dopamine-stimulated inositol phosphate accumulation. These results suggest that melatonin receptors are coupled to dopamine receptor-regulated adenylate cyclase via an inhibitory G protein, and demonstrate another mechanism, in addition to inhibition of dopamine release, through which melatonin can modulate dopaminergic neurotransmission.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adenylate Cyclase Toxin
  • Animals
  • Benzazepines / pharmacology
  • Cells, Cultured
  • Chick Embryo
  • Cyclic AMP / metabolism
  • GTP-Binding Proteins / metabolism
  • Haloperidol / pharmacology
  • Inositol Phosphates / metabolism
  • Melatonin / analogs & derivatives
  • Melatonin / pharmacology
  • Models, Neurological
  • Neurons / physiology*
  • Pertussis Toxin
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology*
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / physiology*
  • Receptors, Melatonin
  • Retina / embryology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Synaptic Transmission / drug effects
  • Virulence Factors, Bordetella / pharmacology


  • Adenylate Cyclase Toxin
  • Benzazepines
  • Inositol Phosphates
  • Receptors, Cell Surface
  • Receptors, Dopamine D1
  • Receptors, Melatonin
  • Virulence Factors, Bordetella
  • 6-chloromelatonin
  • SK&F 82958
  • 2-iodomelatonin
  • Cyclic AMP
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Haloperidol
  • Melatonin
  • 1-Methyl-3-isobutylxanthine