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Activation of muscle nicotinic acetylcholine receptor channels by nicotinic and muscarinic agonists
Author(s) -
Akk Gustav,
Auerbach Anthony
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702941
Subject(s) - oxotremorine , muscarine , chemistry , nicotinic agonist , agonist , muscarinic acetylcholine receptor , nicotinic acetylcholine receptor , acetylcholine receptor , acetylcholine , nicotine , dissociation constant , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m2 , carbachol , endocrinology , biophysics , receptor , medicine , biochemistry , biology
The dose‐response parameters of recombinant mouse adult neuromuscular acetylcholine receptor channels (nAChR) activated by carbamylcholine, nicotine, muscarine and oxotremorine were measured. Rate constants for agonist association and dissociation, and channel opening and closing, were estimated from single‐channel kinetic analysis. The dissociation equilibrium constants were (m M ): ACh (0.16)carbamylcholine (5.1)>oxotremorine M (0.6)>nicotine (0.5)>muscarine (0.15). Rat neuronal α 4 β 2 nAChR can be activated by all of the agonists. However, detailed kinetic analysis was impossible because the recordings lacked clusters representing the activity of a single receptor complex. Thus, the number of channels in the patch was unknown and the activation rate constants could not be determined. Considering both receptor affinity and agonist efficacy, muscarine and oxotremorine are significant agonists of muscle‐type nAChR. The results are discussed in terms of structure‐function relationships at the nAChR transmitter binding site.British Journal of Pharmacology (1999) 128 , 1467–1476; doi: 10.1038/sj.bjp.0702941