| Title | Immunoglobulins (IgGs) from Scleroderma Patients Inhibit Muscarinic Receptor in Internal Anal Sphincter (IAS) Smooth Muscle Cells. | | Author(s) | Singh J, Mehendiratta V, Del Galdo F, Jimenez S, Cohen S, Dimarino A, Rattan S | | Institution | 1Thomas Jefferson University. | | Source | Am J Physiol Gastrointest Liver Physiol 2009 Sep 24. | | Abstract | Systemic Sclerosis (SSc) IgGs affecting M(3)-muscarinic receptor (M(3)-R) have been proposed to be responsible for the GI dysmotility. However, the effect of SSc IgGs on smooth muscle cell (SMC) function has not been studied. We determined the effect of SSc IgGs on the muscarinic receptor activation by bethanechol (BeCh; methyl derivate of carbachol) in SMC and smooth muscle strips from rat IAS. IgGs were purified from GI symptomatic SSc patients and normal volunteers, using protein G-sepharose columns. SMC lengths were determined via computerized digital micrometry. The presence of M(3)-R and IgG-M(3)-R complex was determined by Western blot using LI-COR Odyssey(R) Imaging System. IgGs from SSc patients but not from normal volunteers caused significant and concentration-dependent inhibition of BeCh response (p < 0.05). The maximal shortening of 22.2 +/- 1.2% caused by 10(-4) M BeCh was significantly attenuated to 8.3 +/- 1.2% by 1 mg/ml of SSc IgGs (p < 0.05). Experiments performed in smooth muscle strips revealed a similar effect of SSc IgG which was fully reversible. In contrast to the effect on BeCh, the SSc IgGs caused no significant effect (p > 0.05) on K(+) depolarization, and alpha(1)-adrenoceptor activation by phenylephrine. Western blot studies revealed the specific presence of SSc IgG-M(3)-R complex. SSc IgGs attenuated M3-R activation, which was reversible with antibody removal. These data suggest that SSc gastrointestinal dysmotility may be caused by autoantibodies which inhibit the muscarinic neurotransmission. Future treatment of SSc patients may be directed at the removal or neutralization of these antibodies. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19779020 |
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