Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide

Randa Zakhary, Kenneth D. Poss, Samie R. Jaffrey, Christopher D. Ferris, Susumu Tonegawa, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)14848-14853
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number26
StatePublished - Dec 23 1997

ASJC Scopus subject areas

  • General


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