Submitted on August 9, 2007
Accepted on April 21, 2008
The degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor agonist
Xuefei Li1, Ahmad Azlina2, Mileva Ratko Karabasil2, Nunuk Purwanti2, Takahiro Hasegawa3, Chenjuan Yao2, Tetsuya Akamatsu2, and Kazuo Hosoi2*
1 International Division, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan; Department of Molecular Oral Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima-shi, Tokushima, Japan
2 Department of Molecular Oral Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima-shi, Tokushima, Japan
3 Department of Molecular Oral Physiology, Institute of Health Biosciences, The University of Tokushima Graduate, Tokushima-shi, Tokushima, Japan
* To whom correspondence should be addressed. E-mail: hosoi{at}dent.tokushima-u.ac.jp.
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 weeks. The protein levels of AQP5 and AQP1 were not significantly affected by denervation of the cervical sympathetic trunk (CSTD; sympathectomy). Administration of cevimeline hydrochloride, an M3 muscarinic receptor agonist (10 mg/kg for 7 days, p.o.), but not pilocarpine (0.3 mg/kg for 7 days, p.o.), 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, p.o.), 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.
