Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/2940
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dc.contributor.authorCahusac, Peteren_UK
dc.contributor.authorMavulati, S Cen_UK
dc.date.accessioned2013-06-08T20:22:04Z-
dc.date.available2013-06-08T20:22:04Zen_UK
dc.date.issued2009-10en_UK
dc.identifier.urihttp://hdl.handle.net/1893/2940-
dc.description.abstractPrevious studies suggested that Group I metabotropic glutamate (mGlu) receptors play a role in mechanotransduction processes of slowly adapting type I mechanoreceptors. Using an isolated rat sinus hair follicle preparation we tested a range of compounds. Surprisingly, only non-competitive mGlu1 receptor antagonists produced profound and long-lasting depression of mechanically evoked firing. 6-Amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-α]benzimidazole-2-carboxamide hydrochloride (YM-298198) had an IC50 of 8.7 μM (95% CI 5.7 to 13.2 μM), representing the most potent known blocker of type I mechanoreceptors. The derivative 6-amino-N-cyclohexyl-3-methylthiazolo[3,2-α]benzimidazole-2-carboxamide hydrochloride (desmethyl YM-298198) had a comparable potency. Another compound 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) had a similar depressant effect, although it was less potent with an approximate IC50 of 100 μM. Between three and seven times the concentration of CPCCOEt and YM-298198 respectively was required to produce similar depressions in slowly adapting type II units. No depression, and some weak excitatory effects, were observed using the following ligands: the competitive mGlu1 receptor antagonist α-amino-5-carboxy-3-methyl-2-thiopheneacetic acid (3-MATIDA) (300 μM), the phosphoserine phosphatase inhibitor dl-2-amino-3-phosphonopropionic acid (dl-AP3) (2 mM), non-competitive mGlu5 receptor antagonists 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; (S)-3,5-DHPG, (S)-3,5-dihydroxyphenylglycine (MTEP) (10 μM) and 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) (100 μM), the mGlu1 receptor agonist (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) (500 μM), and the mGlu5 receptor agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) (1 mM). The results suggest that the non-competitive mGlu1 receptor antagonists are not acting at conventional mGlu1 receptors but at other binding sites, possibly those directly associated with mechanogated channels or on any of a number of indirect biochemical pathways. YM-298198 and related compounds may prove to be useful ligands to identify mechanosensitive channel proteins. The selective interference of type I units may provide further evidence that Merkel cells are mechanotransducers. Finally such compounds may deliver insights or treatments for Merkel cell carcinoma.en_UK
dc.language.isoenen_UK
dc.publisherElsevier / International Brain Research Organization (IBRO)en_UK
dc.relationCahusac P & Mavulati SC (2009) Non-competitive metabotropic glutamate 1 receptor antagonists block activity of slowly adapting type I mechanoreceptor units in the rat sinus hair follicle. Neuroscience, 163 (3), pp. 933-941. https://doi.org/10.1016/j.neuroscience.2009.07.015en_UK
dc.rightsThe publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author; you can only request a copy if you wish to use this work for your own research or private study.en_UK
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_UK
dc.subjectMerkel nerve endingsen_UK
dc.subjectmechanogated channelsen_UK
dc.subjectmetabotropic glutamate receptorsen_UK
dc.subjectslowly adapting mechanoreceptorsen_UK
dc.subjectTRP channelsen_UK
dc.subjectTransient Receptor Potential Channelsen_UK
dc.subjectMerkel cell carcinomaen_UK
dc.titleNon-competitive metabotropic glutamate 1 receptor antagonists block activity of slowly adapting type I mechanoreceptor units in the rat sinus hair follicleen_UK
dc.typeJournal Articleen_UK
dc.rights.embargodate3000-01-01en_UK
dc.rights.embargoreason[Cahusac4.pdf] The publisher does not allow this work to be made publicly available in this Repository therefore there is an embargo on the full text of the work.en_UK
dc.identifier.doi10.1016/j.neuroscience.2009.07.015en_UK
dc.citation.jtitleNeuroscienceen_UK
dc.citation.issn0306-4522en_UK
dc.citation.volume163en_UK
dc.citation.issue3en_UK
dc.citation.spage933en_UK
dc.citation.epage941en_UK
dc.citation.publicationstatusPublisheden_UK
dc.citation.peerreviewedRefereeden_UK
dc.type.statusVoR - Version of Recorden_UK
dc.author.emailp.m.b.cahusac@stir.ac.uken_UK
dc.contributor.affiliationPsychologyen_UK
dc.contributor.affiliationGlasgow Caledonian Universityen_UK
dc.identifier.isiWOS:000270284900021en_UK
dc.identifier.scopusid2-s2.0-70149094992en_UK
dc.identifier.wtid811197en_UK
dcterms.dateAccepted2009-10-31en_UK
dc.date.filedepositdate2011-04-14en_UK
rioxxterms.typeJournal Article/Reviewen_UK
rioxxterms.versionVoRen_UK
local.rioxx.authorCahusac, Peter|en_UK
local.rioxx.authorMavulati, S C|en_UK
local.rioxx.projectInternal Project|University of Stirling|https://isni.org/isni/0000000122484331en_UK
local.rioxx.freetoreaddate3000-01-01en_UK
local.rioxx.licencehttp://www.rioxx.net/licenses/under-embargo-all-rights-reserved||en_UK
local.rioxx.filenameCahusac4.pdfen_UK
local.rioxx.filecount1en_UK
local.rioxx.source0306-4522en_UK
Appears in Collections:Psychology Journal Articles

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