Determinants of positive cooperativity between strychnine-like allosteric modulators and N-methylscopolamine at muscarinic receptors.
It has been shown previously that the third extracellular loop (o3) and its vicinity play a critical role in allosteric modulation at muscarinic acetylcholine receptors (mAChRs) (Ellis et al., 1993; Krejçí and Tuçek, 2001; Buller et al., 2002). In this study interaction of four chemically related substances (strychnine, its dimethoxy derivate brucine, precursor for synthesis of strychnine Wieland-Gumlich aldehyde (WGA), and precursor for synthesis of alcuronium propargyl-WGA) with orthosteric antagonist N-methylscopolamine (NMS) was investigated on the M3 subtype of mAChRs mutated at the o3 loop.
Jakubík
Jan
J
Department of Neurochemistry, Institute of Physiology, Academy of Sciences of the Czech Republic, CZ-14220 Prague, Czech Republic. jakubik@biomed.cas.cz
Dolezal
Vladimír
V
D000494:Allosteric Regulation; D019943:Amino Acid Substitution; D001216:Asparagine; D016297:Mutagenesis, Site-Directed; D019832:N-Methylscopolamine / Q000494:pharmacology*; D011392:Proline; D011487:Protein Conformation; D011976:Receptors, Muscarinic / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D012694:Serine; D013331:Strychnine / Q000494:pharmacology*; D013912:Threonine; D014633:Valine
D011976:Receptors, Muscarinic; D013912:Threonine; D012694:Serine; D001216:Asparagine; D011392:Proline; D013331:Strychnine; D014633:Valine; D019832:N-Methylscopolamine