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Development of a radioligand binding assay for 5‐HT 4 receptors in guinea‐pig and rat brain
Author(s) -
Grossman C.J.,
Kilpatrick G.J.,
Bunce K.T.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13617.x
Subject(s) - radioligand , radioligand assay , receptor , guinea pig , striatum , olfactory tubercle , 5 ht receptor , biology , binding site , biochemistry , chemistry , medicine , endocrinology , dopamine , serotonin
1 The 5‐HT 4 receptor antagonist, GR113808, has been radiolabelled to a high specific activity with tritium. 2 Characterization of specific [ 3 H]‐GR113808 binding in homogenates of guinea‐pig striatum and hippocampus revealed a single site of high affinity ( K d values 0.20 and 0.13 n m respectively). 3 [ 3 H]‐GR113808 binding was reversible and displayed rapid kinetics such that association and dissociation were complete within 3 min. 4 Specific [ 3 H]‐GR113808 binding was potently and stereoselectively inhibited by agonists and antagonists acting at the 5‐HT 4 receptor but not by compounds selective for other 5‐HT receptors or other neurotransmitter receptors. 5 Autoradiographic analysis revealed a discrete localization in both guinea‐pig and rat brain with high concentrations of binding in brain areas such as the striatum, substantia nigra and olfactory tubercle. 6 [ 3 H]‐GR113808 binding to homogenates of guinea‐pig striatum meets the criteria for labelling of the 5‐HT 4 receptor and, as such, represents the first characterization of this receptor in a radioligand binding assay.