Effect of 6-methoxy-2-benzoxazolinone on the activities of rat pineal N-acetyltransferase and hydroxyindole-O-methyltransferase and on melatonin production.
A naturally occurring compound, 6-methoxybenzoxazolinone (6-MBOA), present in grasses, has been shown to induce sexual maturation in a number of rodent species. The structural similarity of 6-MBOA and melatonin has led researchers to suspect that 6-MBOA might induce its progonadal effects by directly altering pineal function. Previous studies have shown that 6-MBOA has the properties of a weak beta-adrenergic agonist capable of stimulating rat pineal N-acetyltransferase (NAT) activity at pharmacological concentrations of 10(-3) M. In the present study we have examined the effect of 6-MBOA on both the pineal melatonin synthesizing enzymes, namely, NAT and hydroxyindole-O-methyltransferase (HIOMT) as well as on melatonin production, in organ cultured rat pineal glands. In addition, we have also examined the ability of 6-MBOA to displace a ligand from rat brain alpha- and beta-adrenoceptors. Our results confirm that 6-MBOA stimulates NAT activity and melatonin production at the high concentration of 10(-3) M. It appears to have no effect on HIOMT activity. A competition study shows that 6-MBOA is able of displacing ligands at the alpha- and beta-adrenoceptors but only at concentrations greater than 10(-4) M. Whether such high concentrations of 6-MBOA reach the pineal of rodent in their natural habitat is unknown. However, if 6-MBOA does mediate progonadal effects by altering pineal function it would be expected that 6-MBOA would ultimately inhibit the effects of melatonin. The possibilities are that the high melatonin levels induced by 6-MBOA cause desensitization of melatonin receptors or that 6-MBOA is an antagonist at the level of the melatonin receptor, thus restricting the inhibitory effects of melatonin on the reproductive system.
Daya
S
S
Department of Cellular and Structural Biology, University of Texas, Health Science Center, San Antonio 78284.
Pangerl
B
B
Pangerl
A
A
Troiani
M E
ME
Reiter
R J
RJ
D000121:Acetylserotonin O-Methyltransferase / Q000378:metabolism*; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology*; D001667:Binding, Competitive; D007545:Isoproterenol / Q000494:pharmacology; D008550:Melatonin / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology; D009924:Organ Culture Techniques; D010870:Pineal Gland / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*
D001583:Benzoxazoles; D011941:Receptors, Adrenergic; C031896:6-methoxybenzoxazolinone; D008780:Methyltransferases; D000121:Acetylserotonin O-Methyltransferase; D000123:Acetyltransferases; D008550:Melatonin; D007545:Isoproterenol; D009638:Norepinephrine