Acknowledgments

Research in the laboratory of PMI was supported in part by NIH grant RO1-EY04864.

Figure 6. Effect of SHTP administration on nocturnal melatonin levels in darkness and during acute light exposure. Animals were injected with 5HTP (100mg/kg ip) during dark phase (ZT15). Retinas were dissected 90 minutes later in darkness (night/dark) or following 90min exposure to light (night/light). Melatonin content of the retinas was determined by radioimmunoassay. N = 6-8/group. Light exposure significantly reduced nocturnal melatonin level (p < 0.05). SHTP administration significantly increased melatonin levels relative to vehicle controls in both darkness and during acute light exposure, but the increase was much smaller in light-treated retinas. Tryptophan administration (500mg/kg ip) had no effect on nocturnal melatonin levels. From unpublished data of A.D. Brown, K.B. Thomas, and P.M. Iuvone.

Figure 6. Effect of SHTP administration on nocturnal melatonin levels in darkness and during acute light exposure. Animals were injected with 5HTP (100mg/kg ip) during dark phase (ZT15). Retinas were dissected 90 minutes later in darkness (night/dark) or following 90min exposure to light (night/light). Melatonin content of the retinas was determined by radioimmunoassay. N = 6-8/group. Light exposure significantly reduced nocturnal melatonin level (p < 0.05). SHTP administration significantly increased melatonin levels relative to vehicle controls in both darkness and during acute light exposure, but the increase was much smaller in light-treated retinas. Tryptophan administration (500mg/kg ip) had no effect on nocturnal melatonin levels. From unpublished data of A.D. Brown, K.B. Thomas, and P.M. Iuvone.

Figure 7. Nocturnal tryptophan metabolism in darkness and following light exposure. A. At night, in darkness, TPH and AA-NAT activities are high, resulting in significant metabolism of trptophan (Trp) to melatonin. B. Following acute light exposure, TPH activity, TPH activityremains highbutAA-NAT is inactivated. Asa consequence, metabolism in this pathway is shunted from production of melatonin to 5-hydroxyindolacetic acid (5HIAA), a product of serotonin (5HT) oxidation by monoamine oxidase (MAO).Other abbreviations: AADC = aromatic L-amino acid decarboxylase; HIOMT = hydroxyindole O-methyltransferase; NAS = N-acetylserotonin. Numerical values below 5HTP, 5HT, 5HIAA, and melatonin are steady-state levels expressed in ng/mg protein; values for 5HTP, 5HIAA, and 5HT are from Thomas and Iuvone (38); melatonin values are unpublished data ofA.D. Brown and P.M. Iuvone.

Figure 7. Nocturnal tryptophan metabolism in darkness and following light exposure. A. At night, in darkness, TPH and AA-NAT activities are high, resulting in significant metabolism of trptophan (Trp) to melatonin. B. Following acute light exposure, TPH activity, TPH activityremains highbutAA-NAT is inactivated. Asa consequence, metabolism in this pathway is shunted from production of melatonin to 5-hydroxyindolacetic acid (5HIAA), a product of serotonin (5HT) oxidation by monoamine oxidase (MAO).Other abbreviations: AADC = aromatic L-amino acid decarboxylase; HIOMT = hydroxyindole O-methyltransferase; NAS = N-acetylserotonin. Numerical values below 5HTP, 5HT, 5HIAA, and melatonin are steady-state levels expressed in ng/mg protein; values for 5HTP, 5HIAA, and 5HT are from Thomas and Iuvone (38); melatonin values are unpublished data ofA.D. Brown and P.M. Iuvone.

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