Differential effects of intracellular calcium elevating agents on adrenergic-stimulated cyclic nucleotide and melatonin synthesis in rat pinealocytes.
In this study, the role of elevation of intracellular Ca2+ and activation of protein kinase C on adrenergic-stimulated cyclic nucleotide accumulation and melatonin synthesis in rat pinealocytes was investigated. It was found that whereas KCl, ionomycin, and ouabain, three Ca(2+)-elevating agents, had a potentiating effect on adrenergic-stimulated cyclic AMP response, their effects on melatonin synthesis were inhibitory. Similar inhibition was also observed when dibutyryl cyclic AMP was used to stimulate melatonin synthesis. By determining intracellular Ca2+ directly, it was found that the enhancing effects of these agents on the cyclic AMP response but not their inhibitory effects on melatonin synthesis paralleled their abilities to elevate intracellular Ca2+. In comparison, activation of protein kinase C significantly enhanced the adrenergic-stimulated cyclic AMP response and, to a lesser degree, the adrenergic-stimulated N-acetyltransferase and melatonin levels. These results indicate that (i) Ca(2+)-elevating agents have opposite effects on adrenergic-stimulated cyclic AMP and melatonin production; (ii) a post cyclic AMP event of importance to melatonin synthesis is inhibited by these agents; and (iii) the mechanism of inhibition may not be directly related to their effect on intracellular Ca2+.
Ho
A K
AK
Department of Physiology, University of Alberta, Edmonton, Canada.
Cheng
J
J
Girard
M
M
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004789:Enzyme Activation; D007424:Intracellular Fluid / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D010870:Pineal Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical
D011941:Receptors, Adrenergic; D015759:Ionomycin; D010042:Ouabain; D003994:Bucladesine; D011189:Potassium Chloride; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D011493:Protein Kinase C; D008550:Melatonin; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine