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 ä opioid dipeptide with elevated antagonist activity. We have radiolabelled this compound by catalytic tritiation of the N,N(Me)2-Dmt(39,59-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 af®nity for the ä opioid receptor whereas its binding at ì and k 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 [35S]GTPãS, 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 ä opioid receptors in vitro and in vivo.
Characterization of N,N(Me)(2)-Dmt-Tic-OH, a delta selective opioid dipeptide antagonist
BALBONI, Gianfranco;GUERRINI, Remo;SALVADORI, Severo;
2000
Abstract
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 ä opioid dipeptide with elevated antagonist activity. We have radiolabelled this compound by catalytic tritiation of the N,N(Me)2-Dmt(39,59-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 af®nity for the ä opioid receptor whereas its binding at ì and k 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 [35S]GTPãS, 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 ä opioid receptors in vitro and in vivo.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
