Effect of 6-methoxy-2-benzoxazolinone on the activities of rat pineal N-acetyltransferase and hydroxyindole-O-methyltransferase and on melatonin production

J Pineal Res. 1990;8(1):57-66. doi: 10.1111/j.1600-079x.1990.tb00807.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylserotonin O-Methyltransferase / metabolism*
  • Acetyltransferases / metabolism*
  • Animals
  • Benzoxazoles / pharmacology*
  • Binding, Competitive
  • Isoproterenol / pharmacology
  • Melatonin / metabolism*
  • Methyltransferases / metabolism*
  • Norepinephrine / physiology
  • Organ Culture Techniques
  • Pineal Gland / drug effects
  • Pineal Gland / enzymology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic / metabolism*

Substances

  • Benzoxazoles
  • Receptors, Adrenergic
  • 6-methoxybenzoxazolinone
  • Methyltransferases
  • Acetylserotonin O-Methyltransferase
  • Acetyltransferases
  • Melatonin
  • Isoproterenol
  • Norepinephrine