Activity of cytisine and its brominated isosteres on recombinant human α7, α4β2 and α4β4 nicotinic acetylcholine receptors
Author
dc.contributor.author
Houlihan, Lee M.
Author
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Slater, Yvonne
Author
dc.contributor.author
Guerra, Doris L.
Author
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Peng, Jian Hong
Author
dc.contributor.author
Kuo, Yen Ping
Author
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Lukas, Ronald J.
Author
dc.contributor.author
Cassels Niven, Bruce
Author
dc.contributor.author
Bermudez, Isabel
Admission date
dc.date.accessioned
2018-12-20T14:28:49Z
Available date
dc.date.available
2018-12-20T14:28:49Z
Publication date
dc.date.issued
2001
Cita de ítem
dc.identifier.citation
Journal of Neurochemistry, Volumen 78, Issue 5, 2018, Pages 1029-1043
Identifier
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00223042
Identifier
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10.1046/j.1471-4159.2001.00481.x
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/156157
Abstract
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Effects of cytisine (cy), 3-bromocytisine (3-Br-cy), 5-bromocytisine (5-Br-cy) and 3,5-dibromocytisine (3,5-diBr-cy) on human (h) α7-, α4β2- and α4β4 nicotinic acetylcholine (nACh) receptors, expressed in Xenopus oocytes and cell lines, have been investigated. Cy and its bromo-isosteres fully inhibited binding of both [α-125l]bungarotoxin ([α-125l]BgTx) to hα7- and [3H]cy to hα4β2- or hα4β4-nACh receptors. 3-Br-cy was the most potent inhibitor of both [α-125l]BgTx and [3H]cy binding. Cy was less potent than 3-Br-cy, but 5-Br-cy and 3,5-diBr-cy were the least potent inhibitors. Cy and 3-Br-cy were potent full agonists at hα7-nACh receptors but behaved as partial agonists at hα4β2- and hα4β4-nACh receptors. 5-Br-cy and 3,5-diBr-cy had low potency and were partial agonists at hα7- and hα4β4-nACh receptors, but they elicited no responses on hα4β2-nACh receptors. Cy and 3-Br-cy produced dual dose-response curves (DRC) at both hα4β2- and hα4β4-nACh receptors, but ACh produced dual DRC only a