非表示:
キーワード:
Nicotinic acetylcholine receptor; Muscle, fetal, rat: Patch-clamp; Voltage-clamp: Molecular modelling; Nicotinic agonist; Non-competitive
agonist
要旨:
The fetal rat muscle nicotinic acetylcholine receptor was expressed in Xenopus oocytes. Using the voltage-clamp technique, the
response to a range of agonists was measured, listed in order of (decreasing) activity efficacy: anatoxin >__ epibatidine > acetylcholine >
DMPP (1,1-dimethyl-4-phenylpiperazinium) >> cytisine > pyrantel > nicotine > coniine > tubocurare > lobeline. The agonist responses
were compared with the steric and electrostatic properties of the molecules, using molecular modelling. Single-channel currents were
measured in outside-out patches for acetylcholine, nicotine, cytisine, anatoxin and epibatidine. The conductance of the single channels
was independent of the type of agonist. The mean open times were characteristic of the agonist applied. Tubocurare, better known for its
antagonist properties, was also a partial agonist. Single-channel currents were also observed for tubocurare, and for methyllycaconitine in
patches with a very high density of the muscle nicotinic acetylcholine receptor, and these were blocked by ~x-bungarotoxin. The agonist
properties of physostigmine, galanthamine and their methyl derivatives were also investigated. The conductance of the channels observed
in outside-out patches was similar to that obtained for the classical agonists. The single-channel currents observed for physostigmine,
galanthamine and their methyl derivatives were blocked by a-bungarotoxin, methyllycaconitine and mecamylamine, in contrast to
previously reported studies on neuronal and adult muscle nicotinic acetylcholine receptors.
