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Smooth muscle nitric oxide synthase, co‐localized with caveolin‐1, modulates contraction in mouse small intestine
Author(s) -
ElYazbi Ahmed,
Cho Woo Jung,
Cena Johnathan,
Schulz Richard,
Daniel Edwin
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a808-e
Subject(s) - caveolae , chemistry , medicine , endocrinology , depolarization , nitric oxide synthase , myograph , contraction (grammar) , muscle contraction , caveolin 3 , nitric oxide , microbiology and biotechnology , signal transduction , biology , biochemistry
Neuronal nitric oxide synthase (nNOS) expressed in muscle cells modulates contraction in skeletal and cardiac muscle. In this study, we examine the possible function of nNOS in mouse small intestinal smooth muscle. We examined the tissue response to LNNA (NOS inhibitor) following activation of L‐type calcium channels by depolarization of intact small intestinal segments by KCl. Tissues from control mice responded with an increase in the contractile tone. However, tissues from caveolin‐1 knockout mice, which lacked the nNOS expressed in intestinal smooth muscle upon immunohistochemical examination, did not show a response to LNNA. Immunoprecipiation of caveolin‐1 pulled down nNOS indicating their interaction in smooth muscle membrane. Further, caveolae disruption by cholesterol depletion in control mice led to the loss of caveolin‐1 and nNOS immunoreactivity form smooth muscle membrane and the loss of the tissue response to LNNA. On the other hand, repletion of membrane cholesterol restored nNOS and caveolin‐1 immunoreactivity together with the increase in contractile tone following the treatment with LNNA. The involvement of L‐type calcium channels was examined using nicardipine which blocked the responses to KCl and LNNA. Increasing the intracellular calcium with a SERCA pump inhibitor did not have the same effect as KCl. Blocking soluble guanylate cyclase had the same effect of NOS inhibition while potassium channel blockers did not. We concluded that the activation of nNOS, localized in smooth muscle caveolae, by calcium entering through L‐type calcium channels triggers NO production which modulates the contraction by activation of soluble guanylate cyclase.