Persistent activation of α7 nicotinic ACh receptors associated with stable induction of different desensitized states
dc.contributor.author | Papke, Roger L. | |
dc.contributor.author | Stokes, Clare | |
dc.contributor.author | Damaj, M. Imad | |
dc.contributor.author | Thakur, Ganesh A. | |
dc.contributor.author | Manther, Khan | |
dc.contributor.author | Treinin, Millet | |
dc.contributor.author | Kulkarni, Abhijit R. | |
dc.contributor.author | Horenstein, Nicole A. | |
dc.contributor.buuauthor | Bağdaş, Deniz | |
dc.contributor.department | Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi. | tr_TR |
dc.contributor.researcherid | EOB-5882-2022 | |
dc.contributor.scopusid | 15062425700 | tr_TR |
dc.date.accessioned | 2024-01-25T11:07:24Z | |
dc.date.available | 2024-01-25T11:07:24Z | |
dc.date.issued | 2018-06 | |
dc.description.abstract | Background and Purpose: GAT107 ((3aR,4S,9bS)-4-(4-bromo-phenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta-[c]quinoline-8-sulfonamide) is a positive allosteric modulator (PAM) and agonist of α7 nicotinic acetylcholine receptors (nAChRs)that can cause a prolonged period of primed potentiation of acetylcholine responses after drug washout. NS6740 is a silent agonist of α7 nAChRs that has little or no efficacy for activating the ion channel but induces stable desensitization states, some of which can be converted into channel-active states by PAMs. Although GAT107 and NS6740 appear to stably induce different non-conducting states, both agents are effective treatment for inflammation and inflammatory pain models. We sought to better understand how both of these drugs that have opposite effects on channel activation could regulate signal transduction. Experimental Approach: Voltage-clamp experiments were conducted with α7 nAChRs expressed in Xenopus oocytes. Key Results: Long-lived sensitivity to a PAM or to an agonist was produced by NS6740 or GAT107 respectively. With sequential applications, these two drugs induced varying levels of persistent activation, which is a unique condition for a receptor that is known for rapid desensitization. The non-conducting states induced by NS6740 or GAT107 differ in their sensitivity to an α7 nAChR-selective antagonist and in how effectively they promote current. Conclusions & Implications: Our data suggest that the persistent currents represent a dynamic interconversion between different stable desensitized states and the PAM-inducible conducting states. However, the similarity of NS6740 and GAT107 effects on inflammation and pain suggests that the different stable non-conducting states have common activity on signal transduction. | en_US |
dc.description.sponsorship | United States Department of Health & Human Services National Institutes of Health (NIH) - USA (GM57481) | en_US |
dc.description.sponsorship | US-Israel Binational Science Foundation (2013055) | en_US |
dc.description.sponsorship | United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) (R01CA206028) | en_US |
dc.description.sponsorship | United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of General Medical Sciences (NIGMS) (R01GM057481) | en_US |
dc.identifier.citation | Papke, R. L. vd. (2018). ''Persistent activation of α7 nicotinic ACh receptors associated with stable induction of different desensitized states''. British Journal of Pharmacology, 175(11), 1838-1854. | en_US |
dc.identifier.doi | https://doi.org/10.1111/bph.13851 | |
dc.identifier.endpage | 1854 | tr_TR |
dc.identifier.issn | 0007-1188 | |
dc.identifier.issn | 1476-5381 | |
dc.identifier.issue | 11 | tr_TR |
dc.identifier.pubmed | 28477386 | tr_TR |
dc.identifier.scopus | 2-s2.0-85020305024 | tr_TR |
dc.identifier.startpage | 1838 | tr_TR |
dc.identifier.uri | https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.13851 | |
dc.identifier.uri | https://hdl.handle.net/11452/39325 | |
dc.identifier.volume | 175 | tr_TR |
dc.identifier.wos | 000433567900005 | tr_TR |
dc.indexed.pubmed | PubMed | en_US |
dc.indexed.scopus | Scopus | en_US |
dc.indexed.wos | SCIE | en_US |
dc.language.iso | en | en_US |
dc.publisher | John Wiley and Sons Inc. | en_US |
dc.relation.collaboration | Yurt dışı | tr_TR |
dc.relation.journal | British Journal of Pharmacology | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi | en_US |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.subject | Pharmacology & pharmacy | en_US |
dc.subject | Positive-allosteric-modulation | en_US |
dc.subject | Acetylcholine-receptor | en_US |
dc.subject | Silent agonist | en_US |
dc.subject | Nachr | en_US |
dc.subject | Pharmacology | en_US |
dc.subject | Channel | en_US |
dc.subject | Protein | en_US |
dc.subject | Site | en_US |
dc.subject | Rat | en_US |
dc.subject | Publication | en_US |
dc.subject.emtree | 4 (4 bromo phenyl) 3a,4,5,9b tetrahydro 3h cyclopenta[c]quinoline 8 sulfonamide | en_US |
dc.subject.emtree | Bungarotoxin receptor | en_US |
dc.subject.emtree | Gat 107 | en_US |
dc.subject.emtree | Nicotinic agent | en_US |
dc.subject.emtree | Ns 6740 | en_US |
dc.subject.emtree | Unclassified drug | en_US |
dc.subject.emtree | 1,4-diazabicyclo(3.2.2)nonan-4-yl(5-(3-(trifluoromethyl)phenyl)furan-2-yl)methanone | en_US |
dc.subject.emtree | 4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinoline-8-sulfonamide | en_US |
dc.subject.emtree | Azabicyclo derivative | en_US |
dc.subject.emtree | Bungarotoxin receptor | en_US |
dc.subject.emtree | Furan derivative | en_US |
dc.subject.emtree | Quinoline derivative | en_US |
dc.subject.emtree | Sulfonamide | en_US |
dc.subject.emtree | Allosterism | en_US |
dc.subject.emtree | Analgesic activity | en_US |
dc.subject.emtree | Animal cell | en_US |
dc.subject.emtree | Animal experiment | en_US |
dc.subject.emtree | Animal tissue | en_US |
dc.subject.emtree | Antiinflammatory activity | en_US |
dc.subject.emtree | Article | en_US |
dc.subject.emtree | Clinical effectiveness | en_US |
dc.subject.emtree | Concentration response | en_US |
dc.subject.emtree | Conformation | en_US |
dc.subject.emtree | Controlled study | en_US |
dc.subject.emtree | Desensitization | en_US |
dc.subject.emtree | Drug potentiation | en_US |
dc.subject.emtree | Enzyme activation | en_US |
dc.subject.emtree | Female | en_US |
dc.subject.emtree | Inflammatory pain | en_US |
dc.subject.emtree | Neuropathic pain | en_US |
dc.subject.emtree | Nonhuman | en_US |
dc.subject.emtree | Oocyte | en_US |
dc.subject.emtree | Pain | en_US |
dc.subject.emtree | Priority journal | en_US |
dc.subject.emtree | Protein expression | en_US |
dc.subject.emtree | Signal transduction | en_US |
dc.subject.emtree | Voltage clamp technique | en_US |
dc.subject.emtree | Xenopus laevis | en_US |
dc.subject.emtree | Agonists | en_US |
dc.subject.emtree | Animal | en_US |
dc.subject.emtree | Drug effect | en_US |
dc.subject.emtree | Metabolism | en_US |
dc.subject.mesh | Allosteric Regulation | en_US |
dc.subject.mesh | Alpha7 nicotinic acetylcholine receptor | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Azabicyclo compounds | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Furans | en_US |
dc.subject.mesh | Quinolines | en_US |
dc.subject.mesh | Sulfonamides | en_US |
dc.subject.mesh | Xenopus laevis | en_US |
dc.subject.scopus | Inflammation; Methyllycaconitine; 3-(2,4-Dimethoxybenzylidene)Anabaseine | en_US |
dc.subject.wos | Pharmacology & pharmacy | en_US |
dc.title | Persistent activation of α7 nicotinic ACh receptors associated with stable induction of different desensitized states | en_US |
dc.type | Article | en_US |
dc.wos.quartile | Q1 | en_US |
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