Human 5-HT3A -- Pro 252

Species Original Mutated to Mutation
Human Pro 252  

 

Rat Equivalent Pro 251    
Mouse Equivalent Pro 257

Ala

Gly

Leu

P257A

P257G

P257L

 

mPro257Ala

There was a failure to produce any detectable serotonin responses at -60mV holding potential with <= 1 mM serotonin.
When coupled with the mutations of mVal13'Ser, substantial standing currents were produced. They are changed little by agonists or antagonists. The currents are blocked by the channel blocker TMB-8 at concentrations near those that block Val13'Ser.

Dang H, England PM, Farivar SS, Dougherty DA, Lester HA (2000) Probing the Role of a Conserved M1 Proline Residue in 5-Hydroxtryptamine3 Receptor Gating. Molecular Pharmacology 57:1114-1122

Specific Binding of [3H]granisetron revealed Kd values of 0.27+/- 0.05nM. Using pAb120, the mutant receptor was shown to be localized on the cell surface, however they were non-functional when using whole cell patch clamp.

Deane CM, Lummis SCR (2001) The Role and Predicted Propensity of Conserved Proline Residues in the 5-HT3 Receptor. The Journal of Biological Chemistry 276(41):37962-37966

 

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mPro257Gly

There was a failure to produce any detectable serotonins responses at -60mV holding potential with <= 1 mM serotonin.
Oocytes expressing the mPro261Gly receptor display 2-fold higher specific surface binding ([3H]BRL-43694) than the wild type.
When coupled with the mutations of mVal13'Ser, substantial standing currents were produced. They are changed little by agonists or antagonists. The currents are blocked by the channel blocker TMB-8 at concentrations near those that block Val13'Ser.

Dang H, England PM, Farivar SS, Dougherty DA, Lester HA (2000) Probing the Role of a Conserved M1 Proline Residue in 5-Hydroxtryptamine3 Receptor Gating. Molecular Pharmacology 57:1114-1122

 

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mPro257Leu

There was a failure to produce any detectable serotonin responses at -60mV holding potential with <= 1 mM serotonin.
When coupled with the mutations of mVal13'Ser, substantial standing currents were produced. They are changed little by agonists or antagonists. The currents are blocked by the channel blocker TMB-8 at concentrations near those that block Val13'Ser.

Dang H, England PM, Farivar SS, Dougherty DA, Lester HA (2000) Probing the Role of a Conserved M1 Proline Residue in 5-Hydroxtryptamine3 Receptor Gating. Molecular Pharmacology 57:1114-1122

 

 

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