title: Biochemical and pharmacological characterization of serotonin-O-carboxymethylglycyl[125I]iodotyrosinamide, a new radioiodinated probe for 5-HT1B and 5-HT1D binding sites.
abstract: There is a lack of radioactive probes, particularly radioiodinated probes, for the direct labeling of serotonin-1B (5-HT1B) and serotonin-1D (5-HT1D) binding sites. Serotonin-O-carboxymethylglycyltyrosinamide (S-CM-GTNH2) was shown previously to be specific for these two subtypes; we, therefore, linked a 125I to its tyrosine residue. Biochemical and pharmacological properties of S-CM-G[125I]TNH2-binding sites were studied by quantitative autoradiography on rat and guinea pig brain sections. S-CM-G[125I]TNH2 binding is saturable and reversible with a KD value of 1.3 nM in the rat and 6.4 nM in the guinea pig. Binding is heterogeneous, paralleling the anatomical distribution of 5-HT1B sites in the rat and of 5-HT1D sites in the guinea pig. The binding of 0.02 nM S-CM-G[125I]TNH2 was inhibited by low concentrations of 5-HT, S-CM-GTNH2, CGS 12066 B, 5-methoxytryptamine, and tryptamine in both species. Propranolol inhibited the radioligand binding with a greater affinity in the rat than in the guinea pig. Conversely, 8-hydroxy-2-(di-n-propylamino)tetralin inhibited S-CM-G[125I]TNH2 binding with a greater affinity in the guinea pig than in the rat. Other competitors, specific for 5-HT1C, 5-HT2, 5-HT3, and adrenergic receptors, inhibited S-CM-G[125I]TNH2 binding in rat and guinea pig substantia nigra and in other labeled structures known to contain these receptors, but only at high concentrations. S-CM-G[125I]TNH2 is then a useful new probe for the direct study of 5-HT1B and 5-HT1D binding sites.
authors.affiliation: C.N.R.S., Laboratoire de Neurobiologie E6, Marseille, France.
authors.forename: P
authors.initials: P
authors.lastname: Boulenguez
authors.forename: L
authors.initials: L
authors.lastname: Segu
authors.forename: J
authors.initials: J
authors.lastname: Chauveau
authors.forename: A
authors.initials: A
authors.lastname: Morel
authors.forename: J
authors.initials: J
authors.lastname: Lanoir
authors.forename: M
authors.initials: M
authors.lastname: Delaage
mesh_terms: D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D004151:Dipeptides / Q000737:chemistry*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051381:Rats; D012701:Serotonin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D004151:Dipeptides; D007457:Iodine Radioisotopes; C072128:serotonin-O-carboxymethyl-Gly-Tyr; D012701:Serotonin