Calcium modulates circadian variation in cAMP-stimulated melatonin in chick pineal cells.
In chick pineal cells, melatonin synthesis is regulated by both calcium and cAMP. Calcium-dependent regulation of melatonin is suggested by the monotonic decrease in melatonin observed with decreasing extracellular calcium ion concentrations ([Ca2+]0), the stimulation of melatonin with Bay K8644, and the inhibition of nocturnal melatonin by several calmodulin antagonists. At submicromolar [Ca2+]0, a stimulation of melatonin was observed in the presence of 8-Br cAMP, but not with Bay K8644, suggesting that this amount of stimulation of melatonin by 8-Br cAMP is independent of Ca2+ influx through dihydropyridine-sensitive Ca2+ channels. At micromolar [Ca2+]0, there was a further increase in the stimulation of melatonin by 8-Br cAMP that was not blocked by nifedipine, a dihydropyridine-sensitive Ca2+ channel antagonist. Micromolar [Ca2+]0 is required for the greater stimulation of melatonin by 8-Br cAMP during the night than during the day. Melatonin was stimulated by 8-Br cAMP to higher levels during the night than during the subjective day under normal [Ca2+]0 (1.3 mM). This difference in the amount of melatonin stimulated by 8-Br cAMP during the subjective night versus the subjective day was blocked by lowering [Ca2+]0 to a submicromolar concentration (0.2 microM). Both nifedipine and calmidazolium partially blocked nocturnal increases in melatonin, but were ineffective during the day. These results suggest that Ca2+ plays an important role in the differential ability of cAMP to stimulate melatonin during the night versus the day.
Nikaido
S S
SS
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208-3520, USA.
Takahashi
J S
JS
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002147:Calmodulin / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D008550:Melatonin / Q000096:biosynthesis*; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D011863:Radioimmunoassay
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002147:Calmodulin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D008550:Melatonin; D002118:Calcium