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Pharmacological study on recombinant human GABA-A receptor complex containing alpha5 (leucine155 to valine) combined with beta3gamma2s subunits

  
@article{APS7481,
	author = {Xiu-Kun Wang},
	title = {Pharmacological study on recombinant human GABA-A receptor complex containing alpha5 (leucine155 to valine) combined with beta3gamma2s subunits},
	journal = {Acta Pharmacologica Sinica},
	volume = {22},
	number = {6},
	year = {2016},
	keywords = {},
	abstract = {Aim: To investigate the characterization of the pharmacology of recombinant human GABA-A receptor complex containing alpha5beta3gamma2s subunits, and clarify which amino acids are essential for binding affinity.
Methods: We constructed chimeric subunit of alpha5 (leucine mutated to valine in 155) by site-directed mutation, combined alpha5 or alpha5 (valine 155) with beta3gamma2s subunits by using the baculovirus-transfected Sf-9 insect cell expressing system. Fifteen commercially available effective compounds for the GABA binding recognition site were determined.
Results: We found that competitive antagonist SR95531 and inhibitor Thio-4-piol increased IC50 values about 3 folds in alpha5 (valine155) beta3gamma2s compare to alpha5 (leucine155) beta3gamma2s receptor subunit combinations; Other GABA-A receptor ligands have little difference.
Conclusion: The amino acid residues in 155 is important for the binding affinity and efficacy of SR95531 and Thio-4-piol to GABA-A receptor combinations containing an alpha5 subunit.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/7481}
}