(2S,3R)TMT-L-Tic-OH is a potent inverse agonist at the human delta-opioid receptor.
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.
Hosohata
K
K
Department of Pharmacology, University of Arizona, Tucson 85724, USA.
Burkey
T H
TH
Alfaro-Lopez
J
J
Hruby
V J
VJ
Roeske
W R
WR
Yamamura
H I
HI
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013462:Sulfur Radioisotopes; D044005:Tetrahydroisoquinolines; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D007546:Isoquinolines; D017465:Receptors, Opioid, delta; D013462:Sulfur Radioisotopes; D044005:Tetrahydroisoquinolines; C122084:methyl-2',6'-dimethyltyrosinyltetrahydroisoquinoline-3-carboxylic acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014443:Tyrosine; D004743:Enkephalin, Leucine; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D019204:GTP-Binding Proteins