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(+)‐Anatoxin‐a Is a Potent Agonist at Neuronal Nicotinic Acetylcholine Receptors
Author(s) -
Thomas P.,
Stephens M.,
Wilkie G.,
Amar M.,
Lunt G. G.,
Whiting P.,
Gallagher T.,
Pereira E.,
Alkondon M.,
Albuquerque E. X.,
Wonnacott S.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03519.x
Subject(s) - nicotinic agonist , alpha 4 beta 2 nicotinic receptor , agonist , ganglion type nicotinic receptor , nicotine , chemistry , pharmacology , acetylcholine , acetylcholine receptor , partial agonist , receptor , nicotinic acetylcholine receptor , nicotinic antagonist , biochemistry , neuroscience , biology
The effects of the nicotinic agonist (+)‐anatoxin‐a have been examined in four different preparations, representing at least two classes of neuronal nicotinic receptors. (+)‐Anatoxin‐a was most potent (EC 50 = 48 n M ) in stimulating 86 Rb + influx into M10 cells, which express the nicotinic receptor subtype comprising α4 and β2 subunits. A presynaptic nicotinic receptor mediating acetylcholine release from hippocampal synaptosomes was similarly sensitive to (+)‐anatoxin‐a (EC 50 = 140 n M ). α‐Bungarotoxin‐sensitive neuronal nicotinic receptors, studied using patch‐clamp recording techniques, required slightly higher concentrations of this alkaloid for activation: Nicotinic currents in hippocampal neurons were activated by (+)‐anatoxin‐a with an EC 50 of 3.9 γ M , whereas α7 homooligomers reconstituted in Xenopus oocytes yielded an EC 50 value of 0.58 γ M for (+)‐anatoxin‐a. In these diverse preparations, (+)‐anatoxin‐a was between three and 50 times more potent than (–)‐nicotine and ˜20 times more potent than acetylcholine, making it the most efficacious nicotinic agonist thus far described.