Isoproterenol-induced expression of the cystatin S gene in submandibular glands of parasympathectomized rats

Abstract

Parasympathetic innervation of rat submandibular and parotid glands regulates saliva volume, its rate of secretion and its composition. It also has a regulatory role in hypertrophy and hyperplasia of salivary glands, and in the expression of specific sets of genes. Rat cystatin S is a member of family 2 of the cysteine proteinase inhibitor superfamily. Cystatin S gene expression is tissue- and cell type-specific, temporally regulated during postnatal development, and not observed in adult animals. Isoproterenol (IPR), a β-adrenergic agonist, induces hypertrophic and hyperplastic enlargement of rat salivary glands and 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 the submandibular glands of adult female rats, indicating the participation of sympathetic factor(s) in this regulation. Since both sympathetic and parasympathetic branches of the autonomic nervous system act in parallel in the submandibular gland, it is possible that parasympathetic nerve terminals also provide factor(s) that play a role in regulation of cystatin S gene expression. Experiments described in this paper were designed to test the hypothesis that the parasympathetic nervous system participates in IPR-induced cystatin S gene expression. Bilateral parasympathectomy reduced IPR-induced cystatin S gene expression, suggesting a role of the parasympathetic nervous system in its regulation. Unilateral parasympathectomy in contrast, had no effect on IPR-induced cystatin S gene expression, suggesting that the presence of an intact parasympathetic innervation in the contralateral side permits the `normal' IPR-induced expression of the cystatin S gene in the parasympathectomized gland.