Publication:
Curare alkaloids from matis dart poison: Comparison with d-tubocurarine in interactions with nicotinic, 5-HT3 serotonin and GABAA receptors

Простая страница элемента
dc.contributor.authorSpirova, E. N.
dc.contributor.authorIvanov, I. A.
dc.contributor.authorKasheverov, I. E.
dc.contributor.authorKudryavtsev, D. S.
dc.contributor.authorTsetlin, V. I.
dc.date.accessioned2024-11-19T15:18:54Z
dc.date.available2024-11-19T15:18:54Z
dc.date.issued2019
dc.description.abstract© 2019 Spirova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Several novel bisbenzylisoquinoline alkaloids (BBIQAs) have recently been isolated from a Matis tribe arrow poison and shown by two-electrode voltage-clamp to inhibit mouse muscle nicotinic acetylcholine receptors (nAChR). Here, using radioligand assay with Aplysia californica AChBP and radioiodinated α-bungarotoxin ([125I]-αBgt), we show that BBIQA1, BBIQA2, and d-tubocurarine (d-TC) have similar affinities to nAChR orthosteric site. However, a competition with [125I]-αBgt for binding to the Torpedo californica muscle-type nAChR revealed that BBIQAs1, 2, and 3 are less potent (IC50s = 26.3, 8.75, and 17.0 μM) than d-TC (IC50 = 0.39 μM), while with α7 nAChR in GH4C1 cells, BBIQA1 was less potent that d-TC (IC50s = 162 μM and 7.77 μM, respectively), but BBIQA2 was similar (IC50 = 5.52 μM). In inhibiting the Ca2+ responses induced by acetylcholine in Neuro2a cells expressing the mouse adult α1β1εδ nAChR or human α7 nAChR, BBIQAs1 and 2 had similar potencies to d-TC (IC50s in the range 0.75–3.08 μM). Our data suggest that BBIQA1 and BBIQA2 can inhibit adult muscle α1β1εδ nAChR by both competitive and noncompetitive mechanisms. Further experiments on neuronal α3β2, α4β2, and α9α10 nAChRs, expressed in Xenopus laevis oocytes, showed that similar potencies for BBIQAs1, 2, and d-TC. With α3β2γ2 GABAAR currents were almost completely inhibited by d-TC at a high (100 μM) concentration, but BBIQAs1 and 2 were less potent (only 40–50% inhibition), whereas in competition with Alexa Fluor 546-α-cobratoxin for binding to α1β3γ2 GABAAR in Neuro2a cells, d-TC and these analogs had comparable affinities. Especially interesting effects of BBI-QAs1 and 2 in comparison with d-TC were observed for 5-HT3AR: BBIQA1 and BBIQA2 were 5- and 87-fold less potent than d-TC (IC50 = 22.63 nM). Thus, our results reveal that these BBIQAs differ from d-TC in their potencies towards certain Cys-loop receptors, and we suggest that understanding the reasons behind this might be useful for future drug design.
dc.identifier.citationCurare alkaloids from matis dart poison: Comparison with d-tubocurarine in interactions with nicotinic, 5-HT3 serotonin and GABAA receptors / Spirova, E.N. [et al.] // PLoS ONE. - 2019. - 14. - № 1. - 10.1371/journal.pone.0210182
dc.identifier.doi10.1371/journal.pone.0210182
dc.identifier.urihttps://www.doi.org/10.1371/journal.pone.0210182
dc.identifier.urihttps://www.scopus.com/record/display.uri?eid=2-s2.0-85059494940&origin=resultslist
dc.identifier.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000454952800050
dc.identifier.urihttps://openrepository.mephi.ru/handle/123456789/16431
dc.relation.ispartofPLoS ONE
dc.titleCurare alkaloids from matis dart poison: Comparison with d-tubocurarine in interactions with nicotinic, 5-HT3 serotonin and GABAA receptors
dc.typeArticle
dspace.entity.typePublication
oaire.citation.issue1
oaire.citation.volume14
relation.isOrgUnitOfPublicationc8407a6f-7272-450d-8d99-032352c76b55
relation.isOrgUnitOfPublication.latestForDiscoveryc8407a6f-7272-450d-8d99-032352c76b55
Файлы
Original bundle
Теперь показываю 1 - 1 из 1
Уменьшенное изображение
Name:
W2907268589.pdf
Size:
1.57 MB
Format:
Adobe Portable Document Format
Description:
Download
Коллекции
Публикации