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Biochemical and Pharmacological Characterization of Serotonin‐ O ‐Carboxymethylglycyl[ 125 I]Iodotyrosinamide5 a New Radioiodinated Probe for 5‐HT 1B and 5‐HT 1D Binding Sites
Author(s) -
Boulenguez Pascale,
Segu Louis,
Chauveau Jacques,
Morel Anne,
Lanoir Jeanne,
Delaage Michel
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09348.x
Subject(s) - serotonin , characterization (materials science) , chemistry , 5 ht receptor , stereochemistry , biochemistry , nanotechnology , materials science , receptor
There is a lack of radioactive probes, particularly radioiodinated probes, for the direct labeling of serotonin‐1B (5‐HT 1B ) and serotonin‐ID (5‐HT 1D ) binding sites. Serotonin‐ 0 ‐carboxymethylglycyltyrosinamide (S‐CM‐GTNH 2 ) was shown previously to be specific for these two subtypes; we, therefore, linked a 125 I to its tyrosine residue. Biochemical and pharmacological properties of S‐CM‐G[ 125 I]TNH 2 ‐binding sites were studied by quantitative au‐toradiography on rat and guinea pig brain sections. S‐CM‐G[I25I]TNH 2 binding is saturable and reversible with a KD value of 1.3 n M in the rat and 6.4 n M in the guinea pig. Binding is heterogeneous, paralleling the anatomical distribution of 5‐HT 1B sites in the rat and of 5‐HTD sites in the guinea pig. The binding of 0.02 n M S‐CM‐G[ 125 I]TNH 2 was inhibited by low concentrations of 5‐HT, S‐CM‐GTNH 2 , 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[ 125 I]TNH 2 binding with a greater affinity in the guinea pig than in the rat. Other competitors, specific for 5‐HT,c, 5‐HT2, 5‐HT3, and adrenergic receptors, inhibited S‐CM‐G[ 125 I]TNH 2 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[I25I]TNH 2 is then a useful new probe for the direct study of 5‐HT 1B and 5‐HT 1D binding sites.