Mechanism of melatonin signal transduction in the neonatal rat pituitary.
Melatonin inhibits GnRH-induced LH release from anterior pituitary of the neonatal rat. It acts via specific high affinity receptors and decreases concentrations of intracellular calcium ([Ca2+]i) and cyclic AMP. To determine which of these second messengers transduces the melatonin inhibition of LH release, we have tested the effect of melatonin in the presence of specific drugs affecting either of these second messengers. Calcium channel antagonist nifedipine inhibited LH release from cultured pituitary to a similar degree as did melatonin and prevented the inhibitory effect of melatonin on LH release. Calcium channel agonist. Bay K potentiated the LH release and reduced the inhibitory effect of melatonin. This observation constitutes strong evidence that melatonin inhibits LH release via inhibition of calcium influx through voltage sensitive channels. The cyclic AMP derivative 8-bromo-cAMP potentiated GnRH-stimulation of LH release but did not prevent the melatonin-induced inhibition of the release. However, when used in combination with low concentration of Bay K, which alone reduced the melatonin effect only partially, 8-bromo-cAMP completely blocked the melatonin effect. This observation suggests that both cAMP and [Ca2+]i may be involved in the effect of melatonin on LH release.
Vanecek
J
J
Institute of Physiology, Czechoslovak Academy of Sciences, Prague, Czech Republic.
Klein
D C
DC
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D044094:Receptors, Melatonin; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D011956:Receptors, Cell Surface; D044094:Receptors, Melatonin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007987:Gonadotropin-Releasing Hormone; D000001:Calcimycin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D009543:Nifedipine; D008550:Melatonin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine