TY - JOUR
T1 - Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide
AU - Zakhary, Randa
AU - Poss, Kenneth D.
AU - Jaffrey, Samie R.
AU - Ferris, Christopher D.
AU - Tonegawa, Susumu
AU - Snyder, Solomon H.
PY - 1997/12/23
Y1 - 1997/12/23
N2 - 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 nNOS(Δ/Δ) and HO-2(Δ/Δ) mice. In wild-type mice, NOS inhibitors and HO inhibitors partially inhibited nonadrenergic noncholinergic relaxation. In nNOS(Δ/Δ) animals, NOS inhibitors selectively lost their efficacy, and HO inhibitors were inactive in HO-2(Δ/Δ) animals.
AB - 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 nNOS(Δ/Δ) and HO-2(Δ/Δ) mice. In wild-type mice, NOS inhibitors and HO inhibitors partially inhibited nonadrenergic noncholinergic relaxation. In nNOS(Δ/Δ) animals, NOS inhibitors selectively lost their efficacy, and HO inhibitors were inactive in HO-2(Δ/Δ) animals.
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U2 - 10.1073/pnas.94.26.14848
DO - 10.1073/pnas.94.26.14848
M3 - Article
C2 - 9405702
AN - SCOPUS:0031463819
SN - 0027-8424
VL - 94
SP - 14848
EP - 14853
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 26
ER -