title: Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide.
abstract: Neuronal nitric oxide synthase (nNOS) generates NO in neurons, and heme-oxygenase-2 (HO-2) synthesizes carbon monoxide (CO). We have evaluated the roles of NO and CO in intestinal neurotransmission using mice with targeted deletions of nNOS or HO-2. Immunohistochemical analysis demonstrated colocalization of nNOS and HO-2 in myenteric ganglia. Nonadrenergic noncholinergic relaxation and cyclic guanosine 3',5' monophosphate elevations evoked by electrical field stimulation were diminished markedly in both nNOSDelta/Delta and HO-2(Delta)/Delta mice. In wild-type mice, NOS inhibitors and HO inhibitors partially inhibited nonadrenergic noncholinergic relaxation. In nNOSDelta/Delta animals, NOS inhibitors selectively lost their efficacy, and HO inhibitors were inactive in HO-2(Delta)/Delta animals.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street Baltimore, MD 21205, USA.
authors.forename: R
authors.initials: R
authors.lastname: Zakhary
authors.forename: K D
authors.initials: KD
authors.lastname: Poss
authors.forename: S R
authors.initials: SR
authors.lastname: Jaffrey
authors.forename: C D
authors.initials: CD
authors.lastname: Ferris
authors.forename: S
authors.initials: S
authors.lastname: Tonegawa
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D017615:Enteric Nervous System / Q000502:physiology*; D017353:Gene Deletion; D018390:Gene Targeting; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009569:Nitric Oxide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing)