Document Detail


Activation of transient receptor potential vanilloid subtype 1 increases secretion of the hypofunctional, transplanted submandibular gland.
MedLine Citation:
PMID:  20360133     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyposecretion occurs in most patients early after submandibular gland autotransplantation for severe keratoconjunctivitis sicca. Endogenous transient receptor potential vanilloid subtype 1 (TRPV1) has been recently demonstrated in rabbit submandibular glands, and activation of TRPV1 by capsaicin increases secretion in isolated glands, but the TRPV1-mediated secretory mechanism remains to be elucidated. The purpose of this study was to verify whether activation of TRPV1 by capsaicin could improve the secretion of transplanted gland and its underlying mechanism. The salivary flow of the transplanted glands was significantly decreased, and the mRNA and protein levels of TRPV1 and aquaporin 5 (AQP5) were downregulated in the transplanted glands. Topical capsaicin cream increased secretion and upregulated levels of TRPV1 and AQP5 in transplanted glands. Moreover, in cultured submandibular gland cells, capsaicin increased the mRNA expression of AQP5 and led to redistribution of AQP5 from the cytoplasm to the plasma membrane via TRPV1 activation. Capsaicin enhanced the phosphorylation of extracellular signal-regulated kinase (ERK). Preincubation of cells with PD98059, an inhibitor of ERK kinase, suppressed the capsaicin-induced mRNA expression of AQP5. In summary, the capsaicin-induced secretory mechanism involved activation of TRPV1 and upregulation of AQP5 in an ERK-dependent manner and promoted the redistribution of AQP5 in submandibular gland cells. Activation of TRPV1 may provide a new therapeutic strategy to improve submandibular gland hypofunction.
Authors:
Y Zhang; X Cong; L Shi; B Xiang; Y M Li; Q W Ding; C Ding; L L Wu; G Y Yu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-01
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  299     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-16     Completed Date:  2010-07-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G54-62     Citation Subset:  IM    
Affiliation:
Department of Physiology and Pathophysiology, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, P.R. China. pathophy@bjmu.edu.cn
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MeSH Terms
Descriptor/Qualifier:
Animals
Aquaporin 5 / genetics,  metabolism
Capsaicin / pharmacology*
Cell Membrane / metabolism
Cells, Cultured
Cytoplasm / metabolism
Flavonoids / pharmacology
Male
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors,  metabolism
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors,  metabolism
Phosphorylation
Protein Kinase Inhibitors / pharmacology
Protein Transport
RNA, Messenger / metabolism
Rabbits
Regional Blood Flow
Saliva / secretion*
Salivation / drug effects*
Sensory System Agents / pharmacology*
Submandibular Gland / blood supply,  drug effects*,  metabolism,  secretion,  transplantation*
TRPV Cation Channels / agonists*,  genetics,  metabolism
Time Factors
Transplantation, Autologous
Up-Regulation
Chemical
Reg. No./Substance:
0/Aquaporin 5; 0/Flavonoids; 0/PD 98059; 0/Protein Kinase Inhibitors; 0/RNA, Messenger; 0/Sensory System Agents; 0/TRPV Cation Channels; 404-86-4/Capsaicin; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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