Human 5-HT3B -- Val 277

Species Original Mutated to Mutation
Human Val 277  

 

Rat Equivalent Val 273    
Mouse Equivalent Val 273

Thr

V273T

 

mVal273Thr

Mouse 5-HT3B receptor subunit was expressed in HEK-293 cells with the 5-HT3A subunit.

The TM2 7' position (human V277, mouse V273) is minimally involved in picrotoxin inhibition. The mouse V273T mutation did not significantly impact picrotoxin sensitivity, however, it did result in slightly enhanced 5-HT potency.

When this mutation was combined with mouse N272T, the latter caused an increase in 5-HT potency, and increased picrotoxin sensitivity.

 

Receptor (mouse) 5-HT EC50 (mM) PTX IC50 (mM)
5-HT3A Wild-Type 1.2 +/- 0.07 41.2 +/- 5.6
5-HT3A: S268A (S2'A) 1.0 +/- 0.03* 45.6 +/- 5.2
5-HT3A: T272F (T6'F) 0.9 +/- 0.09* 1900 +/- 300**
5-HT3A: L273T ( L 7'T) 2.0 +/- 0.05** 4.0 +/- 0.5**
5-HT3A/B Wild-Type 1.0 +/- 0.1 1135 +/- 131
5-HT3B: N272T (N6'T) 0.5 +/- 0.03** 213 +/- 24**
5-HT3B: N272S(N6'S) 0.4 +/- 0.01** 173 +/- 28**
5-HT3B: V273T (V7'T) 0.6 +/- 0.09** 866 +/- 35
5-HT3B: N272T, V273T (N6'T,V7'T) 0.4 +/- 0.01** 343 +/- 45**

*Significantly different from the wild-type receptor (p<0.05)

**Significantly different from equivalent wild-type receptor (p<0.01)

Das P, Dillion GH. (2005) Molecular determinants of picrotoxin inhibition of 5-hydroxytryptamine type 3 receptors. The Journal of pharmacology and experimental therapeutics 314(1):320-8

 

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