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Cannabinoid activation of recombinant and endogenous vanilloid receptors.
Eur J Pharmacol 2001; 424(3):211-9EJ

Abstract

The effects of three structurally related cannabinoids on human and rat recombinant vanilloid VR1 receptors expressed in human embryonic kidney (HEK293) cells and at endogenous vanilloid receptors in the rat isolated mesenteric arterial bed were studied. In the recombinant cells, all three were full agonists, causing concentration-dependent increases in [Ca(2+)](i) (FLIPR), with a rank order of potency relative to the vanilloids capsaicin and olvanil, of olvanil> or =capsaicin>AM404 ((allZ)-N-(4-hydroxyphenyl)-5,8,11,14-eicosatetraenamide)>anandamide>methanandamide. These responses were inhibited by the vanilloid VR1 receptor antagonist, capsazepine. In the mesenteric arterial bed, vasorelaxation was evoked by these ligands with a similar order of potency. The AM404-induced vasorelaxation was virtually abolished by capsaicin pretreatment. AM404 inhibition of capsaicin-sensitive sensory neurotransmission was blocked by ruthenium red, but not by cannabinoid CB(1) and CB(2) receptor antagonists. AM404 had no effect on relaxations to calcitonin gene-related peptide. These data demonstrate that the vasorelaxant and sensory neuromodulator properties of AM404 in the rat isolated mesenteric arterial bed are mediated by vanilloid VR1 receptors.

Authors+Show Affiliations

School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK. vera.ralevic@nottingham.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11672565

Citation

Ralevic, V, et al. "Cannabinoid Activation of Recombinant and Endogenous Vanilloid Receptors." European Journal of Pharmacology, vol. 424, no. 3, 2001, pp. 211-9.
Ralevic V, Kendall DA, Jerman JC, et al. Cannabinoid activation of recombinant and endogenous vanilloid receptors. Eur J Pharmacol. 2001;424(3):211-9.
Ralevic, V., Kendall, D. A., Jerman, J. C., Middlemiss, D. N., & Smart, D. (2001). Cannabinoid activation of recombinant and endogenous vanilloid receptors. European Journal of Pharmacology, 424(3), pp. 211-9.
Ralevic V, et al. Cannabinoid Activation of Recombinant and Endogenous Vanilloid Receptors. Eur J Pharmacol. 2001 Jul 27;424(3):211-9. PubMed PMID: 11672565.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid activation of recombinant and endogenous vanilloid receptors. AU - Ralevic,V, AU - Kendall,D A, AU - Jerman,J C, AU - Middlemiss,D N, AU - Smart,D, PY - 2001/10/24/pubmed PY - 2002/1/5/medline PY - 2001/10/24/entrez SP - 211 EP - 9 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 424 IS - 3 N2 - The effects of three structurally related cannabinoids on human and rat recombinant vanilloid VR1 receptors expressed in human embryonic kidney (HEK293) cells and at endogenous vanilloid receptors in the rat isolated mesenteric arterial bed were studied. In the recombinant cells, all three were full agonists, causing concentration-dependent increases in [Ca(2+)](i) (FLIPR), with a rank order of potency relative to the vanilloids capsaicin and olvanil, of olvanil> or =capsaicin>AM404 ((allZ)-N-(4-hydroxyphenyl)-5,8,11,14-eicosatetraenamide)>anandamide>methanandamide. These responses were inhibited by the vanilloid VR1 receptor antagonist, capsazepine. In the mesenteric arterial bed, vasorelaxation was evoked by these ligands with a similar order of potency. The AM404-induced vasorelaxation was virtually abolished by capsaicin pretreatment. AM404 inhibition of capsaicin-sensitive sensory neurotransmission was blocked by ruthenium red, but not by cannabinoid CB(1) and CB(2) receptor antagonists. AM404 had no effect on relaxations to calcitonin gene-related peptide. These data demonstrate that the vasorelaxant and sensory neuromodulator properties of AM404 in the rat isolated mesenteric arterial bed are mediated by vanilloid VR1 receptors. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/11672565/Cannabinoid_activation_of_recombinant_and_endogenous_vanilloid_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299901011530 DB - PRIME DP - Unbound Medicine ER -