info:eu-repo/semantics/article
A conserved arginine with non‐conserved function is a key determinant of agonist selectivity in α7 nicotinic ACh receptors
Fecha
2021-04Registro en:
Minguez Viñas, Teresa; Nielsen, Beatriz Elizabeth; Shoemark, Deborah K.; Gotti, Cecilia; Sessions, Richard B.; et al.; A conserved arginine with non‐conserved function is a key determinant of agonist selectivity in α7 nicotinic ACh receptors; Wiley Blackwell Publishing, Inc; British Journal of Pharmacology; 178; 7; 4-2021; 1651-1668
0007-1188
1476-5381
CONICET Digital
CONICET
Autor
Minguez Viñas, Teresa
Nielsen, Beatriz Elizabeth
Shoemark, Deborah K.
Gotti, Cecilia
Sessions, Richard B.
Mulholland, Adrian J.
Bouzat, Cecilia Beatriz
Wonnacott, Susan
Gallagher, Timothy
Bermudez, Isabel
Oliveira, Ana Sofia
Resumen
The α7 and α4β2* (“*” denotes possibly assembly with another subunit) nicotinic acetylcholine receptors (nAChRs) are the most abundant nAChRs in the mammalian brain. These receptors are the most targeted nAChRs in drug discovery programmes for brain disorders. However, the development of subtype-specific agonists remains challenging due to the high degree of sequence homology and conservation of function in nAChRs. We have developed C(10) variants of cytisine, a partial agonist of α4β2 nAChR that has been used for smoking cessation. The C(10) methyl analogue used in this study displays negligible affinity for α7 nAChR, while retaining high affinity for α4β2 nAChR.