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Am J Physiol Gastrointest Liver Physiol 295: G112-G123, 2008. First published May 1, 2008; doi:10.1152/ajpgi.00359.2007
0193-1857/08 $8.00
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NEUROREGULATION AND MOTILITY

Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor agonist

Xuefei Li, Ahmad Azlina, Mileva Ratko Karabasil, Nunuk Purwanti, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu, and Kazuo Hosoi

Department of Molecular Oral Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima-shi, Tokushima, Japan

Submitted 9 August 2007 ; accepted in final form 21 April 2008

By chorda tympani denervation (CTD, parasympathectomy), the aquaporin 5 (AQP5), but not AQP1, protein level in the rat submandibular gland (SMG) was significantly decreased, dropping to 37% of that of the contralateral gland at 4 wk. The protein levels of AQP5 and AQP1 were not significantly affected by denervation of the cervical sympathetic trunk (sympathectomy). Administration of cevimeline hydrochloride, an M3 muscarinic receptor agonist (10 mg/kg for 7 days po), but not pilocarpine (0.3 mg/kg for 7 days po), recovered the AQP5 protein level reduced by CTD and increased the AQP1 protein level above the control one. The mRNA level of AQP5 was scarcely affected by CTD and cevimeline hydrochloride administration. Administration of chloroquine (50 mg/kg for 7 days po), a denaturant of lysosomes, increased the AQP5 protein level reduced by CTD. An extract obtained from the submandibular lysosomal fraction degraded the AQP5 protein in the total membrane fraction in vitro. These results suggest the possible regulation of the AQP5 protein level in the SMG by the parasympathetic nerves/M3 muscarinic receptor agonist and imply the involvement of lysosomal enzymes, but not a transcriptional mechanism, in this regulation.

aquaporin-5; parasympathectomy; lysosomes; chloroquine


Address for reprint requests and other correspondence: K. Hosoi, Dept. of Molecular Oral Physiology, Institute of Health Biosciences, The Univ. of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8504, Japan (e-mail: hosoi{at}dent.tokushima-u.ac.jp)






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