title: CB1 receptor-mediated respiratory depression by endocannabinoids.
abstract: Endocannabinoids (ECs) are bioactive lipid mediators acting on two distinct cannabinoid receptors (CB1 and CB2), which are ubiquitously expressed in many tissues including the respiratory system. Despite numerous experimental data showing that cannabinomimetics influence respiration, the role of endogenously produced ECs in respiratory control has not been verified yet. Pulse oximetry was used in the present study to directly measure changes in respiratory parameters during elevation of EC levels. The cannabinoid reuptake inhibitor AM-404 (10mgkg-1, i.v.), but not its vehicle, induced a transient reduction of respiratory rate with a concomitant depression of arterial oxygen saturation and increase in breath distension in wild-type mice. In contrast, CB1 knock-out mice showed no alteration in any of these parameters upon administration of AM-404. Our results imply that the EC system has an important role in the physiological control of respiration by modulating the respiratory rate and consequently influencing arterial oxygen saturation. Furthermore, this mechanism is entirely dependent on CB1 receptors.
authors.affiliation: Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary; Max-Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany.
authors.forename: András
authors.initials: A
authors.lastname: Iring
authors.affiliation: Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Hricisák
authors.affiliation: Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary. Electronic address: benyo.zoltan@med.semmelweis-univ.hu.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Benyó
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010092:Oximetry; D010101:Oxygen Consumption / Q000187:drug effects / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency* / Q000235:genetics; D012119:Respiration / Q000187:drug effects / Q000235:genetics; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; C107594:N-(4-hydroxyphenyl)arachidonylamide
keywords: AM-404; CB1 receptor; Endocannabinoids; Pulse oximetry; Respiratory rate