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5‐Methoxytryptamine Inhibits Cyclic AMP Accumulation in Cultured Retinal Neurons Through Activation of a Pertussis Toxin‐Sensitive Site Distinct from the 2‐[ 125 I]Iodomelatonin Binding Site
Author(s) -
Iuvone P. Michael,
Gan Jiwei,
AlonsoGómez Angel L.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64041892.x
Subject(s) - pertussis toxin , forskolin , melatonin , biology , medicine , melatonin receptor , receptor , endocrinology , binding site , g protein , biochemistry
Melatonin and 5‐methoxytryptamine inhibited forskolin‐stimulated cyclic AMP formation in cultured neural cells prepared from embryonic chick retina. Both methoxyindoles exhibited similar potency and efficacy, with EC 50 values of 0.8 n M for melatonin and 7.2 n M for 5‐methoxytryptamine. Inhibition of cyclic AMP formation by 5‐methoxytryptamine or melatonin was prevented by pretreatment with pertussis toxin. Pretreatment of cultures with 5‐methoxytryptamine for 24 h reduced the subsequent inhibitory cyclic AMP response to 5‐methoxytryptamine but not that to 2‐iodomelatonin. Putative melatonin receptors on cultured retinal cells were labeled with 2‐[ 125 I]iodomelatonin. Melatonin displaced specific 2‐[ 125 I]iodomelatonin with a K i value (0.8 n M ) similar to the EC 50 for inhibition of cyclic AMP formation. In contrast, 5‐methoxytryptamine only inhibited 2‐[ 125 I]iodomelatonin binding at very high concentrations ( K i = 650 n M ). Pretreating cultured cells for 24 h with 2‐iodomelatonin or melatonin, but not with 5‐methoxytryptamine, reduced subsequent 2‐[ 125 I]iodomelatonin binding. Thus, 5‐methoxytryptamine appears to inhibit forskolin‐stimulated cyclic AMP formation at a site distinct from the 2‐iodomelatonin binding site.