NDLI: Guanine nucleotide-binding protein regulation of melatonin receptors in lizard brain.

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Guanine nucleotide-binding protein regulation of melatonin receptors in lizard brain.

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Guanine nucleotide-binding protein regulation of melatonin receptors in lizard brain.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Reppert, S. M. Rivkees, S. A. Carlson, L. L.
Description	Author Affiliation: Rivkees SA ( Laboratory of Developmental Chronobiology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.);
Abstract	Melatonin receptors were identified and characterized in crude membrane preparations from lizard brain by using 125I-labeled melatonin (125I-Mel), a potent melatonin agonist. 125I-Mel binding sites were saturable; Scatchard analysis revealed high-affinity and lower affinity binding sites, with apparent Kd of 2.3 +/- 1.0 x 10(-11) M and 2.06 +/- 0.43 x 10(-10) M, respectively. Binding was reversible and inhibited by melatonin and closely related analogs but not by serotonin or norepinephrine. Treatment of crude membranes with the nonhydrolyzable GTP analog guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]), significantly reduced the number of high-affinity receptors and increased the dissociation rate of 125I-Mel from its receptor. Furthermore, GTP[gamma S] treatment of ligand-receptor complexes solubilized by Triton X-100 also led to a rapid dissociation of 125I-Mel from solubilized ligand-receptor complexes. Gel filtration chromatography of solubilized ligand-receptor complexes revealed two major peaks of radio-activity corresponding to Mr greater than 400,000 and Mr ca. 110,000. This elution profile was markedly altered by pretreatment with GTP[gamma S] before solubilization; only the Mr 110,000 peak was present in GTP[gamma S]-pretreated membranes. The results strongly suggest that 125I-Mel binding sites in lizard brain are melatonin receptors, with agonist-promoted guanine nucleotide-binding protein (G protein) coupling and that the apparent molecular size of receptors uncoupled from G proteins is about 110,000.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	86
Language	English
Publisher	National Academy of Sciences
Publisher Date	1989-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Physiology GTP-Binding Proteins Receptors, Neurotransmitter Amphibians Animals Cell Membrane Chromatography, Gel Guanosine 5'-O-(3-Thiotriphosphate) Guanosine Triphosphate Analogs & Derivatives Pharmacology Lizards Membrane Proteins Molecular Weight Receptors, Melatonin Solubility Thionucleotides Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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