PMID- 21441412
OWN - NLM
STAT- MEDLINE
DCOM- 20110916
LR  - 20211020
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 80
IP  - 1
DP  - 2011 Jul
TI  - Desensitization of transient receptor potential ankyrin 1 (TRPA1) by the TRP 
      vanilloid 1-selective cannabinoid arachidonoyl-2 chloroethanolamine.
PG  - 117-23
LID - 10.1124/mol.110.068940 [doi]
AB  - Recent studies on cannabinoid-induced analgesia implicate certain transient 
      receptor potential (TRP) channels as a therapeutic target along with metabotropic 
      cannabinoid receptors. Although TRP ankyrin 1 (TRPA1)-selective cannabinoids, 
      such as (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) 
      pyrrolo-[1,2,3-d,e]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone (WIN55,212), 
      are effective at desensitizing TRPA1 and TRP vanilloid 1 (TRPV1), there is a gap 
      in knowledge in understanding the opposite situation, namely whether 
      TRPV1-selective cannabinoids desensitize TRPA1. We selected the TRPV1-specific 
      synthetic cannabinoid, arachidonoyl-2 chloroethanolamine (ACEA), to study 
      peripheral antihyperalgesic properties because ACEA is known to activate TRPV1. 
      Hence, we used in vitro as well as in vivo assays to evaluate the following: 1) 
      the effects of ACEA on the TRPA1-selective agonist, mustard oil (MO), for 
      calcitonin gene-related peptide (CGRP) release from rat hindpaw skin in vitro; 2) 
      the effects of a peripherally selective dose of ACEA on MO-induced nocifensive 
      behavior in vivo; and 3) the effects of five ACEA-insensitive TRPV1 mutations on 
      ACEA-inhibition of MO-evoked calcium accumulation using a Chinese hamster ovary 
      cell expression system. Our results demonstrate that 1) ACEA significantly 
      attenuated ( approximately 40%) MO-evoked CGRP release from rat hindpaw skin, and this effect 
      was not antagonized by the TRPV1 antagonist, capsazepine; 2) ACEA significantly 
      inhibited ( approximately 40%) MO-induced nocifensive behavior in wild-type mice but not in 
      TRPV1 knockout mice; and 3) all TRPV1 mutations insensitive to ACEA lacked the 
      ability to inhibit MO-evoked calcium accumulation in Chinese hamster ovary cells 
      transfected with TRPV1 and TRPA1. Taken together, the results indicate that a 
      TRPV1-selective cannabinoid, ACEA, inhibits MO-evoked responses via a 
      TRPV1-dependent mechanism. This study strengthens the hypothesis that 
      cannabinoids mediate their peripheral analgesic properties, at least in part, via 
      the TRP channels.
FAU - Ruparel, Nikita B
AU  - Ruparel NB
AD  - Department of Cellular and Structural Biology, University of Texas Health Science 
      Center at San Antonio, Texas 78229, USA.
FAU - Patwardhan, Amol M
AU  - Patwardhan AM
FAU - Akopian, Armen N
AU  - Akopian AN
FAU - Hargreaves, Kenneth M
AU  - Hargreaves KM
LA  - eng
GR  - R01 DE017696/DE/NIDCR NIH HHS/United States
GR  - R01 DE019311/DE/NIDCR NIH HHS/United States
GR  - DE019311/DE/NIDCR NIH HHS/United States
GR  - DE017696/DE/NIDCR NIH HHS/United States
GR  - U54-RR02438/RR/NCRR NIH HHS/United States
GR  - R01 DA019585/DA/NIDA NIH HHS/United States
GR  - DA019585/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110325
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Ankyrins)
RN  - 0 (Arachidonic Acids)
RN  - 0 (Calcium Channels)
RN  - 0 (Endocannabinoids)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (Trpa1 protein, rat)
RN  - 0 (arachidonoyl-2 chloroethanolamine)
SB  - IM
MH  - Animals
MH  - Ankyrins/*antagonists & inhibitors
MH  - Arachidonic Acids/*pharmacology
MH  - Calcium Channels
MH  - Endocannabinoids
MH  - Male
MH  - Mice
MH  - Radioimmunoassay
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TRPA1 Cation Channel
MH  - TRPC Cation Channels
PMC - PMC3127531
EDAT- 2011/03/29 06:00
MHDA- 2011/09/17 06:00
PMCR- 2012/07/01
CRDT- 2011/03/29 06:00
PHST- 2011/03/29 06:00 [entrez]
PHST- 2011/03/29 06:00 [pubmed]
PHST- 2011/09/17 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - mol.110.068940 [pii]
AID - 3692993 [pii]
AID - 10.1124/mol.110.068940 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2011 Jul;80(1):117-23. doi: 10.1124/mol.110.068940. Epub 2011 Mar 
      25.