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dc.contributor.authorBarr, Travis P
dc.contributor.authorAlbrecht, Phillip J.
dc.contributor.authorHou, Quanzhi
dc.contributor.authorMongin, Alexander A.
dc.contributor.authorStrichartz, Gary Richard
dc.contributor.authorRice, Frank L.
dc.date.accessioned2013-05-13T19:22:46Z
dc.date.issued2013
dc.identifier.citationBarr, Travis P., Phillip J. Albrecht, Quanzhi Hou, Alexander A. Mongin, Gary R. Strichartz, and Frank L. Rice. 2013. Air-stimulated ATP release from keratinocytes occurs through connexin hemichannels. PLoS ONE 8(2): e56744.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10622937
dc.description.abstractCutaneous ATP release plays an important role in both epidermal stratification and chronic pain, but little is known about ATP release mechanisms in keratinocytes that comprise the epidermis. In this study, we analyzed ATP release from cultured human neonatal keratinocytes briefly exposed to air, a process previously demonstrated to trigger ATP release from these cells. We show that exposing keratinocytes to air by removing media for 15 seconds causes a robust, long-lasting ATP release. This air-stimulated ATP release was increased in calcium differentiated cultures which showed a corresponding increase in connexin 43 mRNA, a major component of keratinocyte hemichannels. The known connexin hemichannel inhibitors 1-octanol and carbenoxolone both significantly reduced air-stimulated ATP release, as did two drugs traditionally used as ABC transporter inhibitors (glibenclamide and verapamil). These same 4 inhibitors also prevented an increase in the uptake of a connexin permeable dye induced by air exposure, confirming that connexin hemichannels are open during air-stimulated ATP release. In contrast, activity of the MDR1 ABC transporter was reduced by air exposure and the drugs that inhibited air-stimulated ATP release had differential effects on this transporter. These results indicate that air exposure elicits non-vesicular release of ATP from keratinocytes through connexin hemichannels and that drugs used to target connexin hemichannels and ABC transporters may cross-inhibit. Connexins represent a novel, peripheral target for the treatment of chronic pain and dermatological disease.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0056744en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574084/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectSkinen_US
dc.subjectSkin Physiologyen_US
dc.subjectBiochemistryen_US
dc.subjectEnzymesen_US
dc.subjectCoenzymeen_US
dc.subjectNeuroscienceen_US
dc.subjectCognitive Neuroscienceen_US
dc.subjectPainen_US
dc.subjectMedicineen_US
dc.subjectCell Physiologyen_US
dc.subjectAnesthesiologyen_US
dc.subjectDermatologyen_US
dc.subjectDrugs and Devicesen_US
dc.subjectPharmacodynamicsen_US
dc.titleAir-Stimulated ATP Release from Keratinocytes Occurs through Connexin Hemichannelsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorBarr, Travis P
dc.date.available2013-05-13T19:22:46Z
dc.identifier.doi10.1371/journal.pone.0056744*
dash.contributor.affiliatedStrichartz, Gary
dash.contributor.affiliatedBarr, Travis P


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