| First Author | Zhang J | Year | 2006 |
| Journal | Eur J Pharmacol | Volume | 534 |
| Issue | 1-3 | Pages | 77-82 |
| PubMed ID | 16612839 | Mgi Jnum | J:107048 |
| Mgi Id | MGI:3620127 | Doi | 10.1016/j.ejphar.2006.01.049 |
| Citation | Zhang J, et al. (2006) Effects of mutations at conserved TM II residues on ligand binding and activation of mouse 5-HT6 receptor. Eur J Pharmacol 534(1-3):77-82 |
| abstractText | An aspartate residue (Asp-72) in the transmembrane helix II of mouse 5-hydroxytryptamine-6 receptor (5-HT6) is conserved among most G protein-coupled receptors. We have examined the functional significance of this residue by site-directed mutagenesis. A single Asp --> Ala (D72A) mutation resulted in an 8-fold decrease in apparent affinity for 5-HT, and a 60-fold reduction in EC50 value of agonist-induced stimulation of adenylyl cyclase. A F69L/T70I/D72A triple mutant showed a 2-fold reduction in apparent affinity for 5-HT but complete loss of adenylyl cyclase stimulation. Binding of SB-258585 (4-iodo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzene-sulfonamide) , a selective 5-HT6 antagonist, was mildly affected (2- to 4-fold decrease in affinity) in the two mutants. Our data suggest that Asp-72 and additional residues toward the intracellular side of TM II have a limited role in ligand binding but are critical for functional activation of the 5-HT6 receptor. |
