title: Sensitisation of TRPV1 in rat sensory neurones by activation of SNSRs.
abstract: The novel sensory neurone specific receptor (SNSR) family of G-protein coupled receptors are activated by non-opiate fragments of opioid precursor peptides. SNSRs are expressed in nociceptors, and SNSR agonists have been found to cause sensitisation to painful stimuli in vivo. We explored the basis of sensitisation caused by SNSR agonists in sensory neurones by investigating the effect of the SNSR-selective agonist bovine adrenal medulla peptide 8-22 (BAM (8-22)) on gating of the heat and capsaicin-sensitive ion channel TRPV1. Using calcium imaging we found that BAM (8-22) caused sensitisation of the TRPV1 response in approximately 13% of DRG neurones. Sensitisation of TRPV1 in a similar proportion of neurones was observed using whole-cell patch clamping. The PKC-specific inhibitor Ro-31-8220 reduced but did not completely abolish sensitisation, while the protein kinase A inhibitor H-89 was without significant effect. No translocation of the PKC delta, epsilon and zeta isoforms to the cell membrane was observed in response to BAM (8-22). These observations implicate PKC in the sensitisation of TRPV1, but suggest that other pathways are also involved.
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
authors.forename: Stuart Andrew
authors.initials: SA
authors.lastname: Honan
authors.forename: Peter Anthony
authors.initials: PA
authors.lastname: McNaughton
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002417:Cattle; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006358:Hot Temperature; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000187:drug effects / Q000502:physiology*
chemical_list: D007211:Indoles; D007527:Isoenzymes; D007546:Isoquinolines; D011498:Protein Precursors; D013449:Sulfonamides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D004744:Enkephalin, Methionine; C028837:BAM 22P; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002211:Capsaicin; D002118:Calcium; C064758:Ro 31-8220