Human 5-HT3A -- Arg 241
|Rat Equivalent||Arg 246|
|Mouse Equivalent||Arg 246||Ala||R246A|
The mutation was made in the mouse 5-HT3A subunit at Arg246. This residue was numbered Arg222 in the paper in which numbering began at the end of the signal sequence.
The R246A mutation in the mouse 5-HT3A receptor increased the apparent potency of both the full agonist 5-HT (by 5-fold) and the partial agonist 2-Me-5HT (by 12-fold). In addition the mutation converted 2-Me-5HT into a full agonist. Mutant 5-HT3A(R246A) receptors were expressed transiently in HEK 293 cells to study their functional properties using the whole-cell patch clamp technique. This mutation does not change the current-voltage (I-V) relationship for 5-HT or 2-Me-5HT. Moreover, this mutation also converted the 5-HT3A receptor antagonist, apomorphine, to a potent agonist without changing the profile of the competitive antagonist MD72222. Replacing Arg 246 by Ala also increased the rates of 5-HT3A receptor activation and desensitization without affecting deactivation rate.
|EC50(5-HT)||2.7 +/- 0.4 mM||0.5 +/- 0.1 mM|
|EC50(2-Me-5-HT)||14.4 +/- 1.4 mM||1.2 +/- 0.2mM|
|Hill concentration (5-HT)||1.48 +/- 0.08||1.44 +/0.06|
|Hill concentration (2-Me-5HT)||2.48+/- 0.10||1.20 +/- 0.20|
Hu XQ,Zhang L,Stewart RR, Weight FF(2003). Arginine 222 in the pre-transmembrane domain 1 0f 5-HT3A receptors links agonist binding to channel gating.The Journal of biological chemistry 278(47):46583-9
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