Synthesis and binding characteristics of tritiated TIPP[psi], a highly specific and stable delta opioid antagonist.
The pseudopeptide H-Tyr-Tic psi [CH2-NH]Phe-Phe-OH (TIPP[psi]) is a delta opioid antagonist with high delta receptor affinity and unprecedented delta selectivity. TIPP[psi] was radiolabelled by catalytic tritiation of its precursor [Tyr(3',5'-I2)1]TIPP[psi]. The resulting radioligand, [3H]TIPP[psi], had a specific activity of 1.77 TBq/mmol (47.9 Ci/mmol) and showed high stability against enzymatic degradation. [3H]TIPP[psi] binding to rat brain membranes was saturable and Scatchard analysis indicated a single binding site with a Kd of 0.98 nM and a Bmax of 105.4 fmol/mg. A study of [3H]TIPP[psi] binding displacement by various receptor-selective opioids showed the expected rank order of potency (delta >> mu > kappa). [3H]TIPP[psi] represents an excellent new radioligand for delta receptor labelling studies in vitro and in vivo.
Nevin
S T
ST
Institute of Biochemistry, Hungarian Academy of Sciences, Szeged.
Tóth
G
G
Weltrowska
G
G
Schiller
P W
PW
Borsodi
A
A
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D007553:Isotope Labeling; D007700:Kinetics; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D044005:Tetrahydroisoquinolines; D014316:Tritium
D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D044005:Tetrahydroisoquinolines; C092721:tyrosyl-tetrahydroisoquinolinecarbonyl-psi(methylamino)phenylalanyl-phenylalanine; D014316:Tritium; C082263:tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine