Inhaled anandamide reduces leukotriene D4-induced airway obstruction in guinea pigs.
In guinea pigs, we found that intravenous 5,8,11,14-eicosatetraenamide (N-2-hydroxyethyl), arachidonylethanolamide (anandamide), 0.3-10.0 mg/kg, did not inhibit leukotriene D(4) (LTD(4))-induced airway obstruction, while inhaled anandamide, 21.8 and 43.6 microg/kg (estimated inhaled doses), significantly reduced this airway obstructive effect by 24.8+/-8.8 and 42.0+/-11.2%, respectively. In contrast, aerosolized anandamide (43.6 microg/kg) was ineffective against histamine-induced bronchoconstriction. Thus, inhaled, but not intravenous anandamide selectively antagonizes the bronchospasm produced by LTD(4).
Stengel
Peter W
PW
Eli Lilly and Company, Lilly Research Laboratories, 2001 West Main Street, Greenfield, Indiana 46140, USA. stengel_peter_w@lilly.com
Cockerham
Sandra L
SL
Silbaugh
Steven A
SA
D000280:Administration, Inhalation; D000402:Airway Obstruction / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage*; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage; D063388:Endocannabinoids; D006168:Guinea Pigs; D006632:Histamine; D007275:Injections, Intravenous; D017998:Leukotriene D4; D008168:Lung / Q000187:drug effects / Q000502:physiology; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage*
D001095:Arachidonic Acids; D001993:Bronchodilator Agents; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D017998:Leukotriene D4; D006632:Histamine; C078814:anandamide