• PNAS Alerting Services
  • Science Sessions: The PNAS Podcast Program

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

  1. Solomon H. Snyder*§‖
  1. *Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street Baltimore, MD 21205; †Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139-4307; and Department of Medicine, Divisions of ‡Gastroenterology, §Pharmacology and Molecular Sciences, and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205

  1. Contributed by Solomon H. Snyder

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 nNOSΔ/Δ and HO-2Δ/Δ mice. In wild-type mice, NOS inhibitors and HO inhibitors partially inhibited nonadrenergic noncholinergic relaxation. In nNOSΔ/Δ animals, NOS inhibitors selectively lost their efficacy, and HO inhibitors were inactive in HO-2Δ/Δ animals.

Footnotes

    • ↵‖ To whom reprint requests should be addressed. e-mail: sol_snyder{at}qmail.bs-jhu.edu.

  • ABBREVIATIONS

    NOS,
    NO synthase;
    HO,
    heme oxygenase;
    nNOS,
    neuronal NOS;
    cGMP,
    cyclic guanosine 3′,5′ monophosphate;
    NANC,
    nonadrenergic noncholinergic;
    DMPP,
    1,1-dimethyl-4 phenylpiperazinium;
    EFS,
    electrical field stimulation;
    SNP,
    sodium nitroprusside;
    CMV,
    cytomegalovirus;
    SnPP-IX,
    tin protoporphyrin-IX;
    L-NNA,
    NG-nitro-l-arginine;
    LTP,
    long-term potentiation
    • Accepted October 15, 1997.

    Online Impact