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Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide.
Eur J Pharmacol. 2000 Aug 04; 401(2):121-30.EJ

Abstract

We have investigated the inhibition of lipopolysaccharide stimulated nitric oxide production in RAW264.7 macrophages by the cannabinoids and the putative cannabinoid CB(2)-like receptor ligand, palmitoylethanolamide. (R)-(+)-[2, 3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo-[1,2,3-de]-1, 4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate ((+)-WIN55212) and, to a lesser extent (-)-cis-3-[2-hydroxy-4-(1, 1-dimethylheptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexan++ +-1-ol (CP55940), significantly inhibited lipopolysaccharide stimulated nitric oxide production. The level of inhibition was found to be dependent on the concentration of lipopolysaccharide used to induce nitric oxide production. Palmitoylethanolamide significantly inhibited nitric oxide production induced by lipopolysaccharide. The inhibition of nitric oxide production by (+)-WIN55212 but not palmitoylethanolamide was significantly attenuated in the presence of the cannabinoid CB(2) receptor antagonist, N-[(1S)-endo-1,3, 3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazo le- 3-carboxamide (SR144528). (+)-WIN55212 produced a pertussis toxin-sensitive parallel rightward shift in the log concentration-response curve for lipopolysaccharide, causing a fivefold increase in the EC(50) value for lipopolysaccharide with no change in the E(max) value. (-)-WIN55212 had no effect on the log concentration-response curve for lipopolysaccharide. Palmitoylethanolamide did not produce a rightward shift in the lipopolysaccharide concentration-response curve. However, it did produce a pertussis toxin-insensitive reduction in the E(max) value. The results suggest that the inhibition of lipopolysaccharide mediated nitric oxide release by (+)-WIN55212 in murine macrophages is mediated by cannabinoid CB(2) receptors. In contrast, the inhibition by palmitoylethanolamide does not appear to be mediated by cannabinoid receptors.

Authors+Show Affiliations

Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Scotland, Aberdeen, UK. r.ross@abdn.ac.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10924916

Citation

Ross, R A., et al. "Inhibition of Nitric Oxide Production in RAW264.7 Macrophages By Cannabinoids and Palmitoylethanolamide." European Journal of Pharmacology, vol. 401, no. 2, 2000, pp. 121-30.
Ross RA, Brockie HC, Pertwee RG. Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide. Eur J Pharmacol. 2000;401(2):121-30.
Ross, R. A., Brockie, H. C., & Pertwee, R. G. (2000). Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide. European Journal of Pharmacology, 401(2), 121-30.
Ross RA, Brockie HC, Pertwee RG. Inhibition of Nitric Oxide Production in RAW264.7 Macrophages By Cannabinoids and Palmitoylethanolamide. Eur J Pharmacol. 2000 Aug 4;401(2):121-30. PubMed PMID: 10924916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide. AU - Ross,R A, AU - Brockie,H C, AU - Pertwee,R G, PY - 2000/8/5/pubmed PY - 2000/10/14/medline PY - 2000/8/5/entrez SP - 121 EP - 30 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 401 IS - 2 N2 - We have investigated the inhibition of lipopolysaccharide stimulated nitric oxide production in RAW264.7 macrophages by the cannabinoids and the putative cannabinoid CB(2)-like receptor ligand, palmitoylethanolamide. (R)-(+)-[2, 3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo-[1,2,3-de]-1, 4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate ((+)-WIN55212) and, to a lesser extent (-)-cis-3-[2-hydroxy-4-(1, 1-dimethylheptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexan++ +-1-ol (CP55940), significantly inhibited lipopolysaccharide stimulated nitric oxide production. The level of inhibition was found to be dependent on the concentration of lipopolysaccharide used to induce nitric oxide production. Palmitoylethanolamide significantly inhibited nitric oxide production induced by lipopolysaccharide. The inhibition of nitric oxide production by (+)-WIN55212 but not palmitoylethanolamide was significantly attenuated in the presence of the cannabinoid CB(2) receptor antagonist, N-[(1S)-endo-1,3, 3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazo le- 3-carboxamide (SR144528). (+)-WIN55212 produced a pertussis toxin-sensitive parallel rightward shift in the log concentration-response curve for lipopolysaccharide, causing a fivefold increase in the EC(50) value for lipopolysaccharide with no change in the E(max) value. (-)-WIN55212 had no effect on the log concentration-response curve for lipopolysaccharide. Palmitoylethanolamide did not produce a rightward shift in the lipopolysaccharide concentration-response curve. However, it did produce a pertussis toxin-insensitive reduction in the E(max) value. The results suggest that the inhibition of lipopolysaccharide mediated nitric oxide release by (+)-WIN55212 in murine macrophages is mediated by cannabinoid CB(2) receptors. In contrast, the inhibition by palmitoylethanolamide does not appear to be mediated by cannabinoid receptors. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/10924916/Inhibition_of_nitric_oxide_production_in_RAW264_7_macrophages_by_cannabinoids_and_palmitoylethanolamide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(00)00437-4 DB - PRIME DP - Unbound Medicine ER -