12-Hydroperoxyeicosatetraenoic acid (12-HPETE) and 15-HPETE stimulate melatonin synthesis in rat pineals.
The role of arachidonic acid metabolites in norepinephrine (NE)-induced N-acetyltransferase (NAT) activity and melatonin release was examined from 6 h-incubations of rat pineal glands. A cyclooxygenase inhibitor, indomethacin (5 x 10(-8) - 5 x 10(-6) M) was ineffective on melatonin release, in the presence of absence of NE (5 x 10(-6) M) while a lipoxygenase inhibitor, nordihydroguaiaretic acid (5 x 10(-7) -5 x 10(-5) M) had an inhibitory effect. Among the lipoxygenase metabolites, 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and 15-HPETE stimulated both NAT activity and melatonin release in a dose-dependent manner, with a maximal effect occurring at 10(-6) M, while 5-HPETE or hydroxy derivatives of these compounds (12-HETE, 15-HETE and 5-HETE) were ineffective. These results indicate that 12-HPETE and 15-HPETE can be involved in NE-induced melatonin release.
Sakai
K
K
Department of Pharmacology, Asahikawa Medical College, Japan.
Fafeur
V
V
Vulliez-le Normand
B
B
Dray
F
F
D000818:Animals; D015289:Leukotrienes / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D015289:Leukotrienes; D008054:Lipid Peroxides; D014662:Vasoconstrictor Agents; C021201:12-HPETE; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D008550:Melatonin