PT  - JOURNAL ARTICLE
AU  - R S Westphal
AU  - E Sanders-Bush
TI  - Reciprocal binding properties of 5-hydroxytryptamine type 2C receptor agonists and inverse agonists.
DP  - 1994 Nov 01
TA  - Molecular Pharmacology
PG  - 937--942
VI  - 46
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/46/5/937.short
4100  - http://molpharm.aspetjournals.org/content/46/5/937.full
SO  - Mol Pharmacol1994 Nov 01; 46
AB  - Expression of the 5-hydroxytryptamine type 2C (5-HT 2C) receptor in NIH/3T3 fibroblasts results in agonist-independent 5-HT2C receptor activation. Some 5-HT2c receptor antagonists decrease this activation and are termed inverse agonists. The present study uses this system to evaluate functional and receptor binding properties of other 5-HT2C receptor antagonists. A number of inverse agonists, including clozapine, and a neutral antagonist (methysergide) were identified in a functional assay. Guanine nucleotides increased the affinity of a radiolabeled inverse agonist ([3H]mesulergine), suggesting that inverse agonists bind the G protein-uncoupled form of the 5-HT2C receptor with high affinity. Competition binding was performed using conditions that separately labeled the G protein-coupled and -uncoupled forms of the receptor. These studies demonstrated that inverse agonists bound the uncoupled form of the 5-HT2C receptor with higher affinity, compared with the G protein-coupled form. Agonists, on the other hand, had higher affinity for the coupled form whereas neutral antagonists had equal affinity for both forms of the receptor. Thus, 5-HT2C receptor neutral antagonists exhibited functional and receptor binding properties consistent with those of classical receptor antagonists. However, 5-HT2C receptor inverse agonists displayed functional and receptor binding properties that were opposite those of agonists.