Characterization of N,N(Me)2-Dmt-Tic-OH, a delta selective opioid dipeptide antagonist.
N,N(Me)2-Dimethyl-tyrosine-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-OH (N,N(Me)2-Dmt-Tic-OH) is a very selective delta opioid dipeptide with elevated antagonist activity. We have radiolabelled this compound by catalytic tritiation of the N,N(Me)2-Dmt(3',5'-I2)-Tic-OH precursor. The ligand labelled rat brain membranes with a Kd value of 0.42 nM and a Bmax of 63.12 fmol/mg protein. The new tritiated ligand showed high affinity for the delta opioid receptor whereas its binding at mu and kappa opioid receptors was weak. N,N(Me)2-Dmt-Tic-OH was able to inhibit the agonist-stimulated binding of the non-hydrolysable GTP analogue ¿35SGTPgammaS, thus attenuating the activation of G proteins via opioid receptors. This simple opioid dipeptide in both normal and labelled form may serve as a useful tool to study delta opioid receptors in vitro and in vivo.
Monory
K
K
Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged.
Bryant
S D
SD
Kertész
I
I
Balboni
G
G
Guerrini
R
R
Tóth
G
G
Salvadori
S
S
Lazarus
L H
LH
Borsodi
A
A
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D011869:Radioligand Assay; D051381:Rats; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D013462:Sulfur Radioisotopes; D044005:Tetrahydroisoquinolines; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology*
D007546:Isoquinolines; C417742:N,N(Me)2-dimethyl-tyrosine-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-OH; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; D044005:Tetrahydroisoquinolines; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014443:Tyrosine