Submitted on April 18, 2008
Revised on November 28, 2008
Accepted on December 16, 2008
The Autonomic Nervous System Regulates Secretion of Anti-Inflammatory Prohormone SMR1 from Rat Salivary Glands
Katherine Elizabeth Morris1, Chris D. St Laurent1, Ryan S. Hoeve1, Paul Forsythe2, Mavanur R. Suresh1, Ronald D. Mathison3, and Dean Befus1*
1 University of Alberta
2 McMaster University
3 University of Calgary
* To whom correspondence should be addressed. E-mail: dean.befus{at}ualberta.ca.
The autonomic nervous system regulates the secretion of bioactive proteins and peptides from salivary glands that can be important in systemic physiological responses. The prohormone submandibular rat-1 that is highly expressed in rat submandibular glands can be cleaved to produce polypeptides with analgesic and anti-inflammatory activities. Human genes related to submandibular rat-1 have conserved biological functions and are potentially important in pain suppression, erectile function, and inflammation. In this study we describe the differential expression and post-translational modification of submandibular rat-1 protein in salivary glands, the urogenital tract, lung, blood, and saliva in male Sprague-Dawley and Brown Norway rats. Submandibular rat-1 protein is secreted into saliva following the administration of beta-adrenergic or cholinergic agonists. Removal of the sympathetic ganglion that innervates the salivary glands results in increased levels of submandibular rat-1 protein in salivary glands. The secretion of submandibular rat-1 in response to physiological stress may provide a large pool of SMR1-derived peptide products that can promote analgesia and decrease inflammation locally and systemically. This pathway may be conserved among mammals and constitute an important anti-inflammatory and analgesic response to stress.
