title: Autoantibodies in Sjögren's syndrome patients acutely inhibit muscarinic receptor function.
abstract: OBJECTIVE
  Autoantibodies from the sera of Sjögren's syndrome patients (SS IgG) have been suggested to inhibit muscarinic receptor function. However, the acute nature of such an inhibitory effect remains controversial. In this study, we investigated the acute effects of SS IgG on muscarinic receptor function in human submandibular gland (HSG) cells.
  
  
  METHODS
  The effects of autoantibodies on muscarinic receptor function were studied using microspectrofluorimetry, whole-cell patch clamp, immunofluorescence confocal microscopy, and a co-immunoprecipitation assay.
  
  
  RESULTS
  Carbachol (CCh) was found to consistently increase intracellular calcium concentration ([Ca(2+) ](i) ) and activate K(+) current in HSG cells. However, pretreatment of the cells with SS IgG for 5 or 30 min significantly attenuated these responses, with a substantially more prominent effect after 30 min of treatment. Like CCh, adenosine 5'-triphosphate (ATP) also increased [Ca(2+) ](i) and activated K(+) currents in HSG cells, although pretreatment with SS IgG did not affect the cellular response to ATP. CCh was found to reorganize α-fodrin in HSG cells in a Ca(2+) -dependent manner. However, pretreatment with SS IgG prevented the cytoskeletal reorganization of α-fodrin induced by CCh.
  
  
  CONCLUSIONS
  SS IgG acutely and reversibly inhibited muscarinic receptor function, thereby inhibiting the Ca(2+) mobilization necessary for the activation of K(+) currents and α-fodrin reorganization in HSG cells.
authors: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeondong 28, Chongnoku, Seoul 110-749, Korea.
authors: M
authors: M
authors: Jin
authors: S-M
authors: SM
authors: Hwang
authors: N-Y
authors: NY
authors: Koo
authors: B
authors: B
authors: Kim
authors: H-S
authors: HS
authors: Kho
authors: S-Y
authors: SY
authors: Choi
authors: Y W
authors: YW
authors: Song
authors: K
authors: K
authors: Park
mesh_terms: D001323:Autoantibodies / Q000737:chemistry / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D047468:Immunoprecipitation / Q000379:methods; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D015591:Microspectrophotometry / Q000379:methods; D018727:Muscarinic Antagonists / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism*; D013363:Submandibular Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013049:Spectrin
chemical_list: D001323:Autoantibodies; D002118:Calcium; D002217:Carbachol; D002352:Carrier Proteins; D007074:Immunoglobulin G; D008840:Microfilament Proteins; D018727:Muscarinic Antagonists; D024681:Potassium Channels, Calcium-Activated; D011976:Receptors, Muscarinic; D013049:Spectrin