Human 5-HT3A -- Ser 270
|Rat Equivalent||Ser 275|
|Mouse Equivalent||Ser 275||Cys, Ala||S275C, S275A|
Simultaneous mutation of this residue and all other putative phosphorylation sites (replacement by alanine) in the mouse (cloned from NCB-20 cells) 5-HT3A receptor's intracellular loops (TM1-2 and TM3-4) failed to affect modulation by ethanol. Recombinant 5-HT3A receptors were expressed in Xenopus Oocytes (cRNA injection) and 5-HT-evoked currents were recorded using two-electrode voltage-clamp. The effect of replacing all intracellular Ser, Thr and Tyr (by Ala) was to shift the 5-HT concentration-response relationship slightly to the left (more potent).
Machu TK, Coultrap SJ, Waugh MD, Hamilton ME. (1999) Mutation of putative phosphorylation sites in the 5-hydroxytryptamine3 receptor does not eliminate its modulation by ethanol. Alcohol Clin Exp Res. 23(1):12-7
After the application of 1mM MTSET with 10uM 5-HT, there was no significant change. After the application of 1mM MTSES with 10uM 5-HT, there was no significant change.
Reeves DC, Goren EN, Akabas MH, Lummis SCR (2001) Structural and Electrostatic Properties of the 5-HT3 Receptor Pore Revealed by Substituted Cysteine Accessibility Mutagenesis. The Journal of Biological Chemistry 276(45):42035-42042
|EC50||1.67 +/- 0.09||1.62 +/- 0.07|
|Hill Coefficient||2.0 +/- 0.1||3.2 +/- 0.2|
|Mg Inhibition (before MTSET)||-41 +/- 3||-40 +/- 3|
|Mg Inhibition (after MTSET)||-39 +/- 3||-15 +/- 2|
|Deactivation T50 ratio||0.95 +/- 0.03||3.77 +/- 0.79|
Panicker S, Cruz H, Arrabit C, Slesinger PA (2002) Evidence for a Centrally Located Gate in the Pore of a Serotonin-Gated Ion Channel. The Journal of Neuroscience 22(5): 1629-1639
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