QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.067587v1 311/1/411    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duncan, M. Articles by Ralevic, V. Search for Related Content PubMed PubMed Citation Articles by Duncan, M. Articles by Ralevic, V.

CARDIOVASCULAR

Characterization of Cannabinoid Modulation of Sensory Neurotransmission in the Rat Isolated Mesenteric Arterial Bed

School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom

The present study investigated the effects of different classes of cannabinoid (CB) receptor ligands on sensory neurotransmission in the rat isolated mesenteric arterial bed. Electrical field stimulation of the mesenteric bed evoked frequency-dependent vasorelaxation due to the activation of capsaicin-sensitive sensory nerves and release of calcitonin gene-related peptide (CGRP). The CB₁/CB₂ cannabinoid agonists WIN55,212 [(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone] and CP55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol] (0.01–1 µM) attenuated sensory neurogenic relaxation in a concentration-dependent manner. At 0.1 µM, WIN55,212 and CP55,940 were largely ineffective in the presence of the CB₁ antagonists SR141716A [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichloro phenyl)-4-methyl-3-pyrazole-carboxamide] and LY320135 [[6-methoxy-2-(4-methoxyphenyl)benzo[b]-thien-3-yl][4-cyanophenyl] methanone] (1 µM), but their inhibitory actions remained in the presence of the CB₂-selective antagonist SR144528 [N-[1S)-endo-1,3,3,-trimetyl bicyclo [2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide] (1 µM). The CB₁/CB₂ agonist ⁹-tetrahydrocannabinol (THC) (1 µM) attenuated sensory neurogenic relaxations, as did the CB₂ agonist JWH-015 [(2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone]. The inhibitory actions of both THC and JWH-015 were still evident in the presence of SR141716A (1 µM) and SR144528 (1 µM). None of the cannabinoid agonists investigated had an effect on vasorelaxation elicited by exogenous CGRP, indicating a prejunctional mechanism. These data demonstrate that different classes of cannabinoid agonists attenuate sensory neurotransmission via a prejunctional site and provide evidence for mediation by a CB₁ and/or a non-CB₁/CB₂ receptor.

Address correspondence to: Dr. V. Ralevic, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK. E-mail: vera.ralevic{at}nottingham.ac.uk

This article has been cited by other articles:

				B. B. Yao, G. Hsieh, A. V. Daza, Y. Fan, G. K. Grayson, T. R. Garrison, O. El Kouhen, B. A. Hooker, M. Pai, E. J. Wensink, et al. Characterization of a Cannabinoid CB2 Receptor-Selective Agonist, A-836339 [2,2,3,3-Tetramethyl-cyclopropanecarboxylic Acid [3-(2-Methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide], Using in Vitro Pharmacological Assays, in Vivo Pain Models, and Pharmacological Magnetic Resonance Imaging J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 141 - 151. [Abstract] [Full Text] [PDF]

				A. N. Akopian, N. B. Ruparel, A. Patwardhan, and K. M. Hargreaves Cannabinoids Desensitize Capsaicin and Mustard Oil Responses in Sensory Neurons via TRPA1 Activation J. Neurosci., January 30, 2008; 28(5): 1064 - 1075. [Abstract] [Full Text] [PDF]

				N. A. Jeske, A. M. Patwardhan, N. Gamper, T. J. Price, A. N. Akopian, and K. M. Hargreaves Cannabinoid WIN 55,212-2 Regulates TRPV1 Phosphorylation in Sensory Neurons J. Biol. Chem., October 27, 2006; 281(43): 32879 - 32890. [Abstract] [Full Text] [PDF]