Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide.
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.
Zakhary
R
R
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street Baltimore, MD 21205, USA.
Poss
K D
KD
Jaffrey
S R
SR
Ferris
C D
CD
Tonegawa
S
S
Snyder
S H
SH
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
D009569:Nitric Oxide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing)