Melatonin and its precursors in Y79 human retinoblastoma cells: effect of sodium butyrate.
We studied the release of melatonin and the production of its precursors, 5-hydroxytryptophan and serotonin, in cultured Y79 human retinoblastoma cells. This biosynthetic capability was found to be dependent on cell differentiation, which was initiated by culturing Y79 cells for 7 days in dishes coated with poly-D-lysine to promote cell adhesion to the surface of the culture dishes. Differentiation was further induced by exposing the cell monolayer to sodium butyrate (3 mM) for 3 days. This protocol dramatically increased the release of melatonin and the syntheses of 5-hydroxytryptophan and serotonin in response to forskolin stimulation. Exposure to dopamine (10 microM) or L-DOPA (100 microM) markedly diminished the forskolin-stimulated release of melatonin, as well as the production of 5-hydroxytryptophan and serotonin. These observations indicate that Y79 cells represent a primitive cell line which, following appropriate differentiation (e.g. treatment with sodium butyrate) can display biochemical characteristics similar to those of the human retina. Moreover, serotonin synthesis and melatonin release appear to be coupled in Y79 cells. The inhibition of melatonin release by dopamine supports the hypothesis that in these cells, melatonin and dopamine are components of a retinal feedback loop.
Deng
M H
MH
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Lopez G-Coviella
I
I
Lynch
H J
HJ
Wurtman
R J
RJ
D006916:5-Hydroxytryptophan / Q000378:metabolism*; D000704:Analysis of Variance; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005134:Eye Neoplasms; D006801:Humans; D007700:Kinetics; D007980:Levodopa / Q000494:pharmacology; D008550:Melatonin / Q000096:biosynthesis* / Q000378:metabolism; D012175:Retinoblastoma; D012701:Serotonin / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology
D002087:Butyrates; D020148:Butyric Acid; D005576:Colforsin; D012701:Serotonin; D007980:Levodopa; D013134:Spiperone; D006916:5-Hydroxytryptophan; D008550:Melatonin; D004298:Dopamine