Abstract
We examined the pharmacologic effect of beta-methyl-2',6'-dimethyltyrosine-L-tetrahydroisoquinone-3- carboxylic acid ((2S,3R)TMT-L-Tic-OH) on G protein activation in membranes prepared from Chinese Hamster Ovary cells transfected with cDNA of the human delta-opioid receptor. (2S,3R)TMT-L-Tic-OH inhibited G protein activation to 58% of basal with an EC50 of 0.72 nM as determined by [35S]GTPgammaS binding. These findings suggest that (2S,3R)TMT-L-Tic-OH is a highly potent inverse agonist at the human delta-opioid receptor.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CHO Cells
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Cricetinae
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Enkephalin, D-Penicillamine (2,5)- / pharmacology
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Enkephalin, Leucine / analogs & derivatives
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Enkephalin, Leucine / pharmacology
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GTP-Binding Proteins / metabolism
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Humans
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Isoquinolines / pharmacology*
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Membranes / drug effects
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Membranes / metabolism
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Protein Binding / drug effects
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Receptors, Opioid, delta / agonists*
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, delta / metabolism
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Sulfur Radioisotopes
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Tetrahydroisoquinolines*
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Tyrosine / analogs & derivatives*
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Tyrosine / pharmacology
Substances
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Isoquinolines
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Receptors, Opioid, delta
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Sulfur Radioisotopes
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Tetrahydroisoquinolines
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methyl-2',6'-dimethyltyrosinyltetrahydroisoquinoline-3-carboxylic acid
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Guanosine 5'-O-(3-Thiotriphosphate)
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Tyrosine
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Enkephalin, Leucine
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Enkephalin, D-Penicillamine (2,5)-
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N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine
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GTP-Binding Proteins