An immunohistochemistry-based study on aquaporin (AQP)-1, 3, 4, 5 and 8 in the parotid glands, submandibular glands and sublingual glands of Sjögren's syndrome mouse models chronically administered cevimeline.
Cevimeline is a muscarinic agonist that promotes saliva secretion and is used to treat Sjögren's syndrome (SS), an autoimmune disorder in which the exocrine glands that produce saliva are destroyed. Cevimeline is thought to affect the composition of saliva in part by regulating the localization of aquaporins (AQPs). In this study, we investigated the effects of chronic Cevimeline administration in the salivary glands of SS mice on the immunohistochemical localization of aquaporin (AQP)-1, 3, 4, 5 and 8. We used Cevimeline-untreated SS mice, treated SS mice, discontinued SS mice and untreated normal mice. AQP-5 was found in the apical and lateral membranes of acinar cells in the parotid and submandibular glands of cevimeline-treated SS mice and untreated normal mice. Saliva secretion and AQP-5 localization were sustained in SS mice who were chronically administered Cevimeline and at four weeks after discontinuation. Unlike AQP-5, the localization of AQP-1, 3, 4 and 8 were not affected by Cevimeline administration. Our findings demonstrated that administration of Cevimeline maintains the proper localization of AQP-5 in the acinar cells of the salivary gland, which may promote salivation in chronically treated SS mice. Clinically, this suggests that chronic Cevimeline administration may be useful therapeutically for SS patients suffering from a decrease in saliva secretion by improving the disordered AQP-5 localization.
Department of Anatomy, Kurume University School of Medicine.
Moriyoshi
M
Nakamura
Tsuyoshi
T
Saga
Koichi
K
Watanabe
Nagahiro
N
Takahashi
Yoko
Y
Tabira
Jingo
J
Kusukawa
Koh-Ichi
K
Yamaki
D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D051400:Aquaporin 3 / Q000378:metabolism; D051401:Aquaporin 4 / Q000378:metabolism; D051402:Aquaporin 5 / Q000378:metabolism*; D020346:Aquaporins / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010306:Parotid Gland / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011812:Quinuclidines / Q000494:pharmacology*; D012472:Salivation / Q000187:drug effects; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013361:Sublingual Gland / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013363:Submandibular Gland / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors
C496021:Aqp1 protein, mouse; C496028:Aqp3 protein, mouse; C496031:Aqp4 protein, mouse; C496038:Aqp5 protein, mouse; D051401:Aquaporin 4; D051402:Aquaporin 5; D020346:Aquaporins; D018721:Muscarinic Agonists; D011812:Quinuclidines; D013876:Thiophenes; C108330:aquaporin 8; D051398:Aquaporin 1; D051400:Aquaporin 3; C059240:cevimeline