Prostaglandins stimulate serotonin acetylation in chick pineal cells: involvement of cyclic AMP-dependent and calcium/calmodulin-dependent mechanisms.
The effects of prostaglandins (PGs) on the activity of the rate-limiting enzyme of melatonin biosynthesis, arylalkylamine-N-acetyltransferase (NAT) were investigated on primary cultures of dispersed chick pineal cells. In indomethacin-treated cells, PGs caused a four-fold increase in NAT activity. This response was associated with an eight-fold increase in cyclic AMP (cAMP) levels. The potency order of PGs was the same for NAT and for cAMP responses (PGE1 > PGE2 > PGF2 alpha >> cloprostenol). However, each PG tested was 30- to 200-fold more potent to increase NAT activity than to stimulate cAMP accumulation. As a result, half-maximal stimulation of NAT by PGs was not associated with an increase in cAMP levels. Half-maximal stimulation of NAT by PGE1 was highly sensitive to inhibition by a calcium/calmodulin antagonist (W-7). In contrast, maximal stimulation of NAT by PGE1 as well as stimulations evoked by either forskolin or 8-bromo-cAMP were poorly sensitive to inhibition by W-7. These results indicate that an increase in cAMP levels may be responsible for the maximal stimulation of NAT evoked by PGs, whereas half-maximal stimulation of NAT by PGs would rely principally on a calcium/calmodulin-dependent mechanism.
Voisin
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Laboratoire de Neurobiologie et Neuroendocrinologie Cellulaires, URA CNRS 290, UFR Sciences, Poitiers, France.
Van Camp
G
G
Pontoire
C
C
Collin
J P
JP
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000107:Acetylation; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens; D003008:Cloprostenol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*
D002147:Calmodulin; D011453:Prostaglandins; D013449:Sulfonamides; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; D003008:Cloprostenol; C017967:W 7; D015237:Dinoprost; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D000527:Alprostadil; D015232:Dinoprostone; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin