Post by Max on Jun 30, 2005 7:23:39 GMT -5
Synthesis of melatonin
Melatonin, an indoleamine neurohormone that is synthesized mainly in the pineal gland and derived from 5-HT, has many effects on a wide range of physio-pathological functions. Melatonin is synthesized in a pathway in which the first steps involve tryptophan hydroxylation and subsequent decarboxylation. These processes lead to the formation of serotonin (5-HT), which in turn is acetylated on the free amine and then O-methylated on the 5-hydroxyl position. The limiting step of this process is the alkylation of 5-HT, which is catalysed by AANAT. This process takes place mainly in the pineal gland, where AANAT is expressed, despite a recent report suggesting that it is present in other cells, such as mucosal enterochromaffin (EC) cells. Furthermore, melatonin can be synthesized by O-methylation of N-acetyl-5-hydroxytryptamine. This reaction appears to occur in the gut, where high levels of melatonin have been identified, which is not consistent with a pineal production of melatonin. AANAT has been cloned from various species, including humans [1].
Stimulation of melatonin biosynthesis by norepinephrine (NE) depends on the activation of the gene that encodes arylalkylamine N-acetyltransferase (AANAT). Dephosphorylation of pCREB by protein serine/threonine phosphatase (PSPs) is an essential mechanism for downregulation of Aanat transcription in the rat pineal gland [5].
Receptor expression
Some of the effects of melatonin are mediated by the interactions of melatonin with the two melatonin MT(1) and MT(2) receptors [1]. Melatonin has been shown to bind to the MT1 G protein-coupled receptor (GPCR) [2].
The two subtypes of retinoid Z receptor (RZR alpha and beta) and the three splicing variants of retinoid orphan receptor (ROR alpha 1, alpha 2, and alpha 3) form a subfamily within the superfamily of nuclear hormone receptors. It was found that the pineal gland hormone melatonin is a natural ligand of RZR alpha and RZR beta. Ligand-induced transcriptional control is therefore proposed to mediate physiological functions of melatonin in the brain where RZR beta is expressed, but also in peripheral tissues, where RZR alpha was found [4].
Melatonin, an indoleamine neurohormone that is synthesized mainly in the pineal gland and derived from 5-HT, has many effects on a wide range of physio-pathological functions. Melatonin is synthesized in a pathway in which the first steps involve tryptophan hydroxylation and subsequent decarboxylation. These processes lead to the formation of serotonin (5-HT), which in turn is acetylated on the free amine and then O-methylated on the 5-hydroxyl position. The limiting step of this process is the alkylation of 5-HT, which is catalysed by AANAT. This process takes place mainly in the pineal gland, where AANAT is expressed, despite a recent report suggesting that it is present in other cells, such as mucosal enterochromaffin (EC) cells. Furthermore, melatonin can be synthesized by O-methylation of N-acetyl-5-hydroxytryptamine. This reaction appears to occur in the gut, where high levels of melatonin have been identified, which is not consistent with a pineal production of melatonin. AANAT has been cloned from various species, including humans [1].
Stimulation of melatonin biosynthesis by norepinephrine (NE) depends on the activation of the gene that encodes arylalkylamine N-acetyltransferase (AANAT). Dephosphorylation of pCREB by protein serine/threonine phosphatase (PSPs) is an essential mechanism for downregulation of Aanat transcription in the rat pineal gland [5].
Receptor expression
Some of the effects of melatonin are mediated by the interactions of melatonin with the two melatonin MT(1) and MT(2) receptors [1]. Melatonin has been shown to bind to the MT1 G protein-coupled receptor (GPCR) [2].
The two subtypes of retinoid Z receptor (RZR alpha and beta) and the three splicing variants of retinoid orphan receptor (ROR alpha 1, alpha 2, and alpha 3) form a subfamily within the superfamily of nuclear hormone receptors. It was found that the pineal gland hormone melatonin is a natural ligand of RZR alpha and RZR beta. Ligand-induced transcriptional control is therefore proposed to mediate physiological functions of melatonin in the brain where RZR beta is expressed, but also in peripheral tissues, where RZR alpha was found [4].