Melatonin Biosynthesis

Beside the transcriptional up- and downregulation of AANAT, posttranslational processes are also involved in the regulation of rat AANAT activity (27). In the latter investigation the authors showed that AANAT protein is protected by a norepinephrine

p^ receptor norepinephrine I

a1 - receptor

NUCLEUS

AA NAT coding region

NUCLEUS

norepinephrine

p^ receptor norepinephrine I

a1 - receptor

AA NAT coding region

ICER coding region

Figure 10. Scheme of some currently known signal transduction pathways in the rodent pineal gland. ER, endoplasmatic reticulum; HIOMT, hydroxyindole-O-methyl-transferase. The other abbreviations are explained in the text. Modified after 61,39).

ICER coding region

Figure 10. Scheme of some currently known signal transduction pathways in the rodent pineal gland. ER, endoplasmatic reticulum; HIOMT, hydroxyindole-O-methyl-transferase. The other abbreviations are explained in the text. Modified after 61,39).

cAMP-mediated inhibition of proteasomal proteolysis and that intact protein is indispensable for activity. Consequently the amount of AANAT protein determines the level of AANAT activity. In dispersed rat pinealocytes NE-treatment leads to a time-dependent upregulation of AANAT protein and melatonin biosynthesis (Figure 8). AANAT protein was not detectable in untreated cells and those treated for 2 h with NE, but rose linearly between 2 and 6 hours after stimulation and reached a plateau which lasted for at least another six hours. The amount of melatonin in the medium showed a different kinetic; it rose slowly but steadily during the first six hours after stimulation and then showed a steeper and linear increase during the following six hours (Figure 8). Interestingly, we found that in C3H mice the melatonin increase in the medium after NE-stimulation is even more delayed than in rats (Von Gall et al., unpublished observations; see above).

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