Phe369(7.38) at human 5-HT(7) receptors confers interspecies selectivity to antagonists and partial agonists.

ABSTRACT:

Background and purpose

Human and rat 5-HT(7) receptors were studied with a particular emphasis on the molecular interactions involved in ligand binding, searching for an explanation to the interspecies selectivity observed for a set of compounds. We performed affinity studies, molecular modelling and site-directed mutagenesis, with special focus on residue Phe(7.38) of the human 5-HT(7) receptor [Cys(7.38) in rat].

Experimental approach

Competition binding studies were performed for seven 5-HT(7) receptor ligands at three different 5-HT(7) receptors. The functional behaviour was evaluated by measuring 5-carboxytryptamine-stimulated cAMP production. Computational simulations were carried out to explore the structural bases in ligand binding observed for these compounds.

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SUBMITTER: Varin T 

PROVIDER: S-EPMC2839265 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature