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Publication : Differential Contribution of TRPA1, TRPV4 and TRPM8 to Colonic Nociception in Mice.

First Author  Mueller-Tribbensee SM Year  2015
Journal  PLoS One Volume  10
Issue  7 Pages  e0128242
PubMed ID  26207981 Mgi Jnum  J:311634
Mgi Id  MGI:6253749 Doi  10.1371/journal.pone.0128242
Citation  Mueller-Tribbensee SM, et al. (2015) Differential Contribution of TRPA1, TRPV4 and TRPM8 to Colonic Nociception in Mice. PLoS One 10(7):e0128242
abstractText  BACKGROUND: Various transient receptor potential (TRP) channels in sensory neurons contribute to the transduction of mechanical stimuli in the colon. Recently, even the cold-sensing menthol receptor TRPM(melastatin)8 was suggested to be involved in murine colonic mechano-nociception. METHODS: To analyze the roles of TRPM8, TRPA1 and TRPV4 in distension-induced colonic nociception and pain, TRP-deficient mice and selective pharmacological blockers in wild-type mice (WT) were used. Visceromotor responses (VMR) to colorectal distension (CRD) in vivo were recorded and distension/pressure-induced CGRP release from the isolated murine colon ex vivo was measured by EIA. RESULTS: Distension-induced colonic CGRP release was markedly reduced in TRPA1-/- and TRPV4-/- mice at 90/150 mmHg compared to WT. In TRPM8-deficient mice the reduction was only distinct at 150 mmHg. Exposure to selective pharmacological antagonists (HC030031, 100 muM; RN1734, 10 muM; AMTB, 10 muM) showed corresponding effects. The unselective TRP blocker ruthenium red (RR, 10 muM) was as efficient in inhibiting distension-induced CGRP release as the unselective antagonists of mechanogated DEG/ENaC (amiloride, 100 muM) and stretch-activated channels (gadolinium, 50 muM). VMR to CRD revealed prominent deficits over the whole pressure range (up to 90 mmHg) in TRPA1-/- and TRPV4-/- but not TRPM8-/- mice; the drug effects of the TRP antagonists were again highly consistent with the results from mice lacking the respective TRP receptor gene. CONCLUSIONS: TRPA1 and TRPV4 mediate colonic distension pain and CGRP release and appear to govern a wide and congruent dynamic range of distensions. The role of TRPM8 seems to be confined to signaling extreme noxious distension, at least in the healthy colon.
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