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The cannabinomimetic arachidonyl-2-chloroethylamide (ACEA) acts on capsaicin-sensitive TRPV1 receptors but not cannabinoid receptors in rat joints.
Br J Pharmacol. 2004 Aug; 142(8):1361-7.BJ

Abstract

The vasoactive effects of the synthetic cannabinoid (CB) arachidonyl-2-chloroethylamide (ACEA) was tested in the knee joints of urethane-anaesthetised rats. Experiments were also performed to determine whether these vasomotor responses could be blocked by the selective CB(1) receptor antagonists AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) (10(-9) mol) and AM281 (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide) (10(-8) mol), as well as the selective CB(2) receptor antagonist AM630 (6-iodo-2-methyl-1-[2-4(morpholinyl)ethyl]-[1H-indol-3-yl](4-methoxyphenyl)methanone) (10(-8) mol). Peripheral application of ACEA (10(-14)-10(-9) mol) onto the exposed surface of the knee joint capsule caused a dose-dependent increase in synovial blood flow. The dilator action of the CB occurred within 1 min after drug administration and rapidly returned to control levels shortly thereafter. The maximal vasodilator effect of ACEA corresponded to a 30% increase in articular perfusion compared to control levels. The hyperaemic action of ACEA was not significantly altered by coadministration of AM251, AM281 or AM630 (P>0.05; two-way ANOVA). The transient receptor potential channel vanilloid receptor 1 (TRPV(1)) antagonist capsazepine (10(-6) mol) significantly reduced the vasodilator effect of ACEA on joint blood vessels (P=0.002). Furthermore, destruction of unmyelinated and thinly myelinated joint sensory nerves by capsaicin (8-methyl-N-vanillyl-6-nonenamide) treatment also attenuated ACEA responses (P<0.0005). These data clearly demonstrate a vasodilator effect of the cannabinomimetic ACEA on knee joint perfusion. Rather than a classic CB receptor pathway, ACEA exerts its vasomotor influence by acting via TRPV(1) receptors located on the terminal branches of capsaicin-sensitive afferent nerves innervating the joint.

Authors+Show Affiliations

Department of Physiology and Biophysics, 3300, Hospital Drive NW, University of Calgary, Calgary, Alberta, Canada T2N 4N1.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15277316

Citation

Baker, Chris L., and Jason J. McDougall. "The Cannabinomimetic Arachidonyl-2-chloroethylamide (ACEA) Acts On Capsaicin-sensitive TRPV1 Receptors but Not Cannabinoid Receptors in Rat Joints." British Journal of Pharmacology, vol. 142, no. 8, 2004, pp. 1361-7.
Baker CL, McDougall JJ. The cannabinomimetic arachidonyl-2-chloroethylamide (ACEA) acts on capsaicin-sensitive TRPV1 receptors but not cannabinoid receptors in rat joints. Br J Pharmacol. 2004;142(8):1361-7.
Baker, C. L., & McDougall, J. J. (2004). The cannabinomimetic arachidonyl-2-chloroethylamide (ACEA) acts on capsaicin-sensitive TRPV1 receptors but not cannabinoid receptors in rat joints. British Journal of Pharmacology, 142(8), 1361-7.
Baker CL, McDougall JJ. The Cannabinomimetic Arachidonyl-2-chloroethylamide (ACEA) Acts On Capsaicin-sensitive TRPV1 Receptors but Not Cannabinoid Receptors in Rat Joints. Br J Pharmacol. 2004;142(8):1361-7. PubMed PMID: 15277316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The cannabinomimetic arachidonyl-2-chloroethylamide (ACEA) acts on capsaicin-sensitive TRPV1 receptors but not cannabinoid receptors in rat joints. AU - Baker,Chris L, AU - McDougall,Jason J, Y1 - 2004/07/26/ PY - 2004/7/28/pubmed PY - 2005/1/27/medline PY - 2004/7/28/entrez SP - 1361 EP - 7 JF - British journal of pharmacology JO - Br J Pharmacol VL - 142 IS - 8 N2 - The vasoactive effects of the synthetic cannabinoid (CB) arachidonyl-2-chloroethylamide (ACEA) was tested in the knee joints of urethane-anaesthetised rats. Experiments were also performed to determine whether these vasomotor responses could be blocked by the selective CB(1) receptor antagonists AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) (10(-9) mol) and AM281 (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide) (10(-8) mol), as well as the selective CB(2) receptor antagonist AM630 (6-iodo-2-methyl-1-[2-4(morpholinyl)ethyl]-[1H-indol-3-yl](4-methoxyphenyl)methanone) (10(-8) mol). Peripheral application of ACEA (10(-14)-10(-9) mol) onto the exposed surface of the knee joint capsule caused a dose-dependent increase in synovial blood flow. The dilator action of the CB occurred within 1 min after drug administration and rapidly returned to control levels shortly thereafter. The maximal vasodilator effect of ACEA corresponded to a 30% increase in articular perfusion compared to control levels. The hyperaemic action of ACEA was not significantly altered by coadministration of AM251, AM281 or AM630 (P>0.05; two-way ANOVA). The transient receptor potential channel vanilloid receptor 1 (TRPV(1)) antagonist capsazepine (10(-6) mol) significantly reduced the vasodilator effect of ACEA on joint blood vessels (P=0.002). Furthermore, destruction of unmyelinated and thinly myelinated joint sensory nerves by capsaicin (8-methyl-N-vanillyl-6-nonenamide) treatment also attenuated ACEA responses (P<0.0005). These data clearly demonstrate a vasodilator effect of the cannabinomimetic ACEA on knee joint perfusion. Rather than a classic CB receptor pathway, ACEA exerts its vasomotor influence by acting via TRPV(1) receptors located on the terminal branches of capsaicin-sensitive afferent nerves innervating the joint. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/15277316/The_cannabinomimetic_arachidonyl_2_chloroethylamide__ACEA__acts_on_capsaicin_sensitive_TRPV1_receptors_but_not_cannabinoid_receptors_in_rat_joints_ L2 - https://doi.org/10.1038/sj.bjp.0705902 DB - PRIME DP - Unbound Medicine ER -