Melatonin signal transduction in hamster brain: inhibition of adenylyl cyclase by a pertussis toxin-sensitive G protein

Endocrinology. 1989 Nov;125(5):2670-6. doi: 10.1210/endo-125-5-2670.


Melatonin signal transduction was examined in median eminence/pars tuberalis (ME/PT) explants from Djungarian hamsters. High affinity melatonin receptors in hamster ME/PT were first quantified by in vitro autoradiography using the potent melatonin agonist 125I-labeled melatonin ([125I]MEL). Scatchard analysis of [125I]MEL binding in ME/PT revealed high affinity receptors [dissociation constant (Kd) = 2.75 X 10(-11) M]. [125I]MEL binding was markedly reduced by guanine nucleotides; treatment with the nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) caused a 10-fold decrease in receptor affinity. Melatonin (10 nM) significantly inhibited forskolin-stimulated cAMP accumulation in ME/PT, but not in pituitary or pineal glands. In ME/PT explants, melatonin and 6-chloromelatonin inhibited forskolin-stimulated cAMP accumulation in a dose-dependent manner with similar potency (significant inhibition for each at concentrations greater than or equal to 100 pM). Serotonin significantly inhibited forskolin-stimulated cAMP levels only at doses greater than or equal to 100 microM. Inhibition of [125I]MEL binding in ME/PT by these three indolamines paralleled that determined for inhibition of forskolin-stimulated cAMP accumulation. Pertussis toxin treatment (1 microgram/ml) blocked the ability of melatonin (10 nM) to inhibit forskolin-stimulated cAMP accumulation and significantly reduced [125I]MEL binding. Pertussis toxin ADP-ribosylated the alpha-subunits of at least two guanine nucleotide-binding proteins in ME/PT explants with molecular weights of approximately 40 K. Melatonin did not increase phosphodiesterase activity in ME/PT explants. The results strongly suggest that a signal transduction pathway for melatonin in mammals involves inhibition of adenylyl cyclase by a pertussis toxin-sensitive guanine nucleotide-binding protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylate Cyclase Toxin*
  • Adenylyl Cyclase Inhibitors*
  • Animals
  • Brain / drug effects
  • Brain / enzymology
  • Brain / physiology*
  • Cricetinae
  • Cyclic AMP / metabolism
  • GTP-Binding Proteins / physiology*
  • Kinetics
  • Melatonin / physiology*
  • Organ Culture Techniques
  • Pertussis Toxin*
  • Receptors, Melatonin
  • Receptors, Neurotransmitter / physiology*
  • Signal Transduction* / drug effects
  • Virulence Factors, Bordetella / pharmacology*


  • Adenylate Cyclase Toxin
  • Adenylyl Cyclase Inhibitors
  • Receptors, Melatonin
  • Receptors, Neurotransmitter
  • Virulence Factors, Bordetella
  • Cyclic AMP
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Melatonin