Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/2940
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dc.contributor.authorCahusac, Peter-
dc.contributor.authorMavulati, S C-
dc.date.accessioned2013-06-08T20:22:04Z-
dc.date.issued2009-10-
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.isoen-
dc.publisherElsevier / International Brain Research Organization (IBRO)-
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.-
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.-
dc.subjectMerkel nerve endingsen_UK
dc.subjectmechanogated channelsen_UK
dc.subjectmetabotropic glutamate receptorsen_UK
dc.subjectslowly adapting mechanoreceptorsen_UK
dc.subject.lcshTRP channels-
dc.subject.lcshTransient Receptor Potential Channels-
dc.subject.lcshMerkel cell carcinoma-
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.embargodate2999-12-31T00:00:00Z-
dc.rights.embargoreasonThe 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.-
dc.identifier.doihttp://dx.doi.org/10.1016/j.neuroscience.2009.07.015-
dc.citation.jtitleNeuroscience-
dc.citation.issn0306-4522-
dc.citation.volume163-
dc.citation.issue3-
dc.citation.spage933-
dc.citation.epage941-
dc.citation.publicationstatusPublished-
dc.citation.peerreviewedRefereed-
dc.type.statusPublisher version (final published refereed version)-
dc.author.emailp.m.b.cahusac@stir.ac.uk-
dc.contributor.affiliationPsychology-
dc.contributor.affiliationGlasgow Caledonian University-
dc.rights.embargoterms2999-12-31-
dc.rights.embargoliftdate2999-12-31-
dc.identifier.isi000270284900021-
Appears in Collections:Psychology Journal Articles

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