title: Hypersensitive mAChRs are involved in the epiphora of transplanted glands.
abstract: Autologous transplantation of the submandibular gland is an effective treatment for severe dry eye syndrome. However, more than 40% of patients experience epiphora 3 to 6 months after transplantation. The underlying mechanism of epiphora remains to be elucidated. To investigate the potential roles of muscarinic acetylcholine receptors (mAChRs) in the induction of epiphora in transplanted glands, we assessed and found elevated mRNA and protein expression of M1- and M3-mAChR in transplanted glands from epiphora patients. The content of inositol 1, 4, 5-trisphosphate was also elevated. Moreover, carbachol (5 and 10 µM) induced greater increase of [Ca(2+)]i in isolated epiphora submandibular cells than in controls. Although aquaporin-5 (AQP5) content and distribution in the apical and lateral plasma of epiphora glands did not change, AQP5 content was reduced in lipid microdomains (lipid rafts and caveolae) but increased in non-lipid microdomains compared with controls. Carbachol (10 µM) increased the ratio of non-lipid microdomain to total AQP5 in the cultured control submandibular gland tissue. Taken together, these results indicated that hypersensitive mAChRs might be involved in the epiphora of transplanted submandibular glands by modulating AQP5 trafficking.
authors.affiliation: Center Laboratory and Center for Salivary Gland Diseases, Peking University School and Hospital of Stomatology, 22 Zhong Guan Cun South St., Beijing, 100081, P.R. China.
authors.forename: C
authors.initials: C
authors.lastname: Ding
authors.forename: X
authors.initials: X
authors.lastname: Cong
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: N Y
authors.initials: NY
authors.lastname: Yang
authors.forename: S L
authors.initials: SL
authors.lastname: Li
authors.forename: L L
authors.initials: LL
authors.lastname: Wu
authors.forename: G Y
authors.initials: GY
authors.lastname: Yu
mesh_terms: D000328:Adult; D051402:Aquaporin 5 / Q000032:analysis; D064592:Autografts / Q000187:drug effects / Q000637:transplantation*; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D021941:Caveolae / Q000187:drug effects / Q000473:pathology; D015352:Dry Eye Syndromes / Q000601:surgery*; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis; D007766:Lacrimal Apparatus Diseases / Q000209:etiology*; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D011183:Postoperative Complications; D043643:Receptor, Muscarinic M1 / Q000032:analysis; D043587:Receptor, Muscarinic M3 / Q000032:analysis; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013363:Submandibular Gland / Q000187:drug effects / Q000637:transplantation*; D046509:Tissue Culture Techniques; D055815:Young Adult
chemical_list: C496036:AQP5 protein, human; D051402:Aquaporin 5; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol
keywords: aquaporin 5; lipid raft; muscarinic acetylcholine receptor; secretion; submandibular gland; transplantation