| Autor: |
HERRICK-DAVIS, K., GRINDE, E., GAUTHIER, C., TEITLER, M. |
| Zdroj: |
Annals of the New York Academy of Sciences; December 1998, Vol. 861 Issue: 1 p140-145, 6p |
| Abstrakt: |
Previous studies from our laboratory have shown that the 5-HT2Cserotonin receptor can be rendered constitutively active by changing amino acid 312 (third intracellular loop) from serine to lysine (S312K). In the present study, detailed radioligand binding analyses were performed to characterize the constitutively activated state of S312K mutant receptors. All agonists tested displayed high affinity for both [3H]5-HT and [3H]mesulergine binding to S312K receptors, but displayed low affinity for [3H]mesulergine binding to native 5-HT2Creceptors. [3H]5-HT labeled the same total number of S312K binding sites as [3H]mesulergine. 5-HT2Cantagonists inhibited S312K basal inositol phosphate production. These results suggest that S312K receptors mimic the active conformation of native 5-HT2Creceptors and provide a good model system for evaluating drugs for inverse agonist activity. Also, S312K receptors may represent a new system for screening 5-HT2Cagonist activity by comparing [3H]mesulergine binding to native and S312K mutant receptors. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Plný text