title: Muscarinic acetylcholine receptor-mediated tight junction opening is involved in epiphora in late phase of submandibular gland transplantation.
abstract: Submandibular gland (SMG) autotransplantation is an effective therapy for treating severe dry eye syndrome. However, epiphora occurs in more than 40% of patients 6 months after operation. We previously found that muscarinic acetylcholine receptor (mAChR) plays a crucial role in regulating SMG secretion partially through the modulation on tight junction (TJ)-based paracellular pathway. Therefore, the present study aimed to investigate the possible involvement of mAChR and TJ in a rabbit long-term model of SMG transplantation. We found that SMG secretion was significantly increased on postoperative days 90 and 180, which imitated epiphora observed in the patients with SMG transplantation. Although the mRNA expression and fluorescence intensity of M1 and M3 mAChR subtypes were reversed to control levels on postoperative days 30, 90, and 180, the content of β-arrestin2, but not β-arrestin1, was gradually decreased after transplantation, which suggests that mAChR may be hypersensitive in late phase of SMG transplantation. The width of acinar TJs was enlarged and fluorescence intensity of F-actin in peri-apicolateral membranes were remarkably increased on postoperative days 90 and 180. Topical treatment with atropine gel significantly reduced SMG secretion, TJ width, as well as F-actin intensity in peri-apicolateral membranes on postoperative days 180. Moreover, in a perfused rabbit SMG, carbachol increased salivary secretion, enlarged TJ width, and induced F-actin rearrangement, whereas these responses were inhibited by atropine pretreatment. Taken together, our findings suggest that the hypersensitive mAChR may contribute to epiphora in late phase of SMG transplantation through modulating TJ-based paracellular permeability.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, People's Republic of China.|Department of Pediatric Dentistry, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, 100050, People's Republic of China.
authors.forename: Ning-Yan
authors.initials: NY
authors.lastname: Yang
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, People's Republic of China.
authors.forename: Chong
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, People's Republic of China.
authors.forename: Ruo-Lan
authors.initials: RL
authors.lastname: Xiang
authors.affiliation: Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, People's Republic of China.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Wu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, People's Republic of China.
authors.forename: Guang-Yan
authors.initials: GY
authors.lastname: Yu
authors.affiliation: Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, People's Republic of China. congxin634@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Cong
mesh_terms: D000199:Actins; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D064592:Autografts; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability; D007766:Lacrimal Apparatus Diseases / Q000209:etiology*; D023421:Models, Animal; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000502:physiology*; D012469:Salivary Glands / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism / Q000637:transplantation*; D019108:Tight Junctions / Q000473:pathology*
chemical_list: D000199:Actins; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol
keywords: Muscarinic acetylcholine receptor; Secretion; Submandibular gland; Tight junction; Transplantation