Autonomic regulation of cystatin S gene expression in rat submandibular glands

Innervation of rat submandibular and parotid glands by the autonomic nervous system regulates saliva volume, its rate of secretion and its composition. The autonomic nervous system also plays a regulatory role in the differentiation and growth of salivary glands, and in the expression of specific sets of genes. Rat cystatin S, a member of family 2 of the cysteine proteinase inhibitor superfamily, is expressed in submandibular and parotid glands of human and rat. In the rat, cystatin S gene expression is tissue- and cell type-specific, is temporally regulated during postnatal development, and not observed in adult animals. The beta-adrenergic agonist isoproterenol (IPR) induces hypertrophic and hyperplastic enlargements of rat salivary glands and the expression of a number of genes including cystatin S. Sympathectomy reduces, but does not completely block, IPR-induced expression of the cystatin S gene in submandibular glands of adult female rats, indicating the participation of sympathetic factor(s) in its regulation. Bilateral parasympathectomy also reduces IPR-induced cystatin S gene expression, suggesting a role of the parasympathetic nervous system in its regulation. Experiments described in this paper suggest that similar factor(s) arising from both the sympathetic and parasympathetic branches of the autonomic nervous system simultaneously participate in IPR-induced cystatin S gene expression in submandibular glands.