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Characterization of cannabinoid modulation of sensory neurotransmission in the rat isolated mesenteric arterial bed.
J Pharmacol Exp Ther. 2004 Oct; 311(1):411-9.JP

Abstract

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 CB(1)/CB(2) 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 microM) attenuated sensory neurogenic relaxation in a concentration-dependent manner. At 0.1 microM, WIN55,212 and CP55,940 were largely ineffective in the presence of the CB(1) 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 microM), but their inhibitory actions remained in the presence of the CB(2)-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 microM). The CB(1)/CB(2) agonist Delta(9)-tetrahydrocannabinol (THC) (1 microM) attenuated sensory neurogenic relaxations, as did the CB(2) 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 microM) and SR144528 (1 microM). 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 CB(1) and/or a non-CB(1)/CB(2) receptor.

Authors+Show Affiliations

School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15205450

Citation

Duncan, Marnie, et al. "Characterization of Cannabinoid Modulation of Sensory Neurotransmission in the Rat Isolated Mesenteric Arterial Bed." The Journal of Pharmacology and Experimental Therapeutics, vol. 311, no. 1, 2004, pp. 411-9.
Duncan M, Kendall DA, Ralevic V. Characterization of cannabinoid modulation of sensory neurotransmission in the rat isolated mesenteric arterial bed. J Pharmacol Exp Ther. 2004;311(1):411-9.
Duncan, M., Kendall, D. A., & Ralevic, V. (2004). Characterization of cannabinoid modulation of sensory neurotransmission in the rat isolated mesenteric arterial bed. The Journal of Pharmacology and Experimental Therapeutics, 311(1), 411-9.
Duncan M, Kendall DA, Ralevic V. Characterization of Cannabinoid Modulation of Sensory Neurotransmission in the Rat Isolated Mesenteric Arterial Bed. J Pharmacol Exp Ther. 2004;311(1):411-9. PubMed PMID: 15205450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of cannabinoid modulation of sensory neurotransmission in the rat isolated mesenteric arterial bed. AU - Duncan,Marnie, AU - Kendall,David A, AU - Ralevic,Vera, Y1 - 2004/06/17/ PY - 2004/6/19/pubmed PY - 2004/12/16/medline PY - 2004/6/19/entrez SP - 411 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 311 IS - 1 N2 - 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 CB(1)/CB(2) 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 microM) attenuated sensory neurogenic relaxation in a concentration-dependent manner. At 0.1 microM, WIN55,212 and CP55,940 were largely ineffective in the presence of the CB(1) 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 microM), but their inhibitory actions remained in the presence of the CB(2)-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 microM). The CB(1)/CB(2) agonist Delta(9)-tetrahydrocannabinol (THC) (1 microM) attenuated sensory neurogenic relaxations, as did the CB(2) 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 microM) and SR144528 (1 microM). 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 CB(1) and/or a non-CB(1)/CB(2) receptor. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15205450/Characterization_of_cannabinoid_modulation_of_sensory_neurotransmission_in_the_rat_isolated_mesenteric_arterial_bed_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15205450 DB - PRIME DP - Unbound Medicine ER -