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Mechanisms of ligand binding and efficacy at the human D 2(short) dopamine receptor
Author(s) -
Payne Sarah L.,
Johansson Anette M.,
Strange Philip G.
Publication year - 2002
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 - 10.1046/j.1471-4159.2002.01046.x
Subject(s) - agonist , partial agonist , spiperone , chemistry , receptor , ligand (biochemistry) , potency , binding site , stereochemistry , pharmacology , medicine , biochemistry , biology , in vitro
Mechanisms of ligand binding and receptor activation for the human D 2(short) dopamine receptor have been probed using two homologous series of monohydroxylated and dihydroxylated agonists (phenylethylamines and 2‐dipropylaminotetralins). In ligand binding studies, the majority of compounds exhibited competition curves versus [ 3 H]spiperone that were best fitted using a two site binding model. The compounds had different abilities (potencies and maximal effects) to stimulate [ 35 S]GTPγS binding and to inhibit forskolin‐stimulated cAMP accumulation. From the data it can be concluded that: (i) the ability of an agonist to stabilize receptor/G protein coupling can be used to predict agonist efficacy for some groups of compounds (2‐dipropylaminotetralins) but not for others (phenylethylamines); (ii) the receptor may be activated by unhydroxylated compounds; (iii) single hydroxyl groups or pairs of hydroxyl groups on the agonist may contribute tobinding affinity, potency and efficacy; and (iv) for the 2‐dipropylaminotetralin series two modes of agonist/receptor interaction have been identified associated with different relative efficacy.