Effects of cannabinoid receptor ligands on LPS-induced pulmonary inflammation in mice.
The effects of cannabinoid receptor agonists WIN 55,212-2, delta9-tetrahydrocannabinol (delta9-THC), arachidonoylethanolamide (anandamide) and palmitoylethanolamide on lipopolysaccharide (LPS) -induced bronchopulmonary inflammation in mice were investigated. WIN 55,212-2 and delta9-THC induced a concentration-dependent decrease in TNF-alpha level in the bronchoalveolar lavage fluid (BALF) (maximum inhibition 52.7% and 36.9% for intranasal doses of 750 nmol x kg(-1) and 2.65 mmol x kg(-1), respectively). This effect was accompanied by moderately reduced neutrophil recruitment. Palmitoylethanolamide (750 nmol x kg(-1)) diminished the level of TNF-alpha in BALF by 31.5% but had no effect on neutrophil recruitment. Anandamide (7.5-750 nmol x kg(-1)) did not influence the inflammatory process but TNF-alpha level and neutrophil recruitment were decreased by 28.0% and 62.0%, respectively, with 0.075 nmol x kg(-1). These results demonstrate that the cannabinoid receptor ligands inhibited LPS-induced pulmonary inflammation and suggest that this effect could be at least in part mediated by the cannabinoid CB2 receptor.
Berdyshev
E
E
Institute of Marine Biology, Vladivostok, Russia.
Boichot
E
E
Corbel
M
M
Germain
N
N
Lagente
V
V
D000577:Amides; D000818:Animals; D001095:Arachidonic Acids / Q000627:therapeutic use; D048588:Benzoxazines; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D063388:Endocannabinoids; D004983:Ethanolamines; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000627:therapeutic use; D009281:Naphthalenes / Q000627:therapeutic use; D009504:Neutrophils / Q000473:pathology; D010169:Palmitic Acids / Q000627:therapeutic use; D011014:Pneumonia / Q000139:chemically induced* / Q000517:prevention & control*; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000577:Amides; D001095:Arachidonic Acids; D048588:Benzoxazines; D063388:Endocannabinoids; D004983:Ethanolamines; D008070:Lipopolysaccharides; D009025:Morpholines; D009281:Naphthalenes; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014409:Tumor Necrosis Factor-alpha; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C005958:palmidrol; C078814:anandamide