Cystatin S: Molecular biology and sympathetic innervation

The rat submandibular glands (SMG) are innervated by both sympathetic and the parasympathetic branches of the autonomic nervous system which, in turn, regulate the secretory functions of the glands. Parasympathetic innervation of rat SMG is present at birth, whereas sympathetic nerve fibers reach the glands by postnatal day 5. Isoproterenol (IPR), a β-adrenoreceptor agonist, induces hypertrophic and hyperplastic enlargements of rat salivary glands, and induces the expression of a number of genes, including cystatin S, a member of family 2 of the cystein proteinase inhibitor superfamily. Cystatin S genes expression is tisuue- and cell-type specific, occurs transiently during development, and is not observed in adult animals. Sympathetic denervation of adult SMG, achieved by removing the superior cervical ganglion, reduces the induction of the cystatin S gene by a single injection of IPR. In addition, recent data indicate that the β receptors present early in the developing SMG are functional and are capable of responding to IPR by increasing the expression of the cystatin S gene, even when sympathetic nerve fibers have not reached the gland. The level of IPR-induced cystatin S mRNA remains constant until day 8, at which time a dramatic induction of cystatin S mRNA is observed. This statistically significant increase in cystatin S mRNA at day 8 was diminished, but not completely suppressed, upon sympathectomy of one day old animals. These data indicate that an intact sympathetic innervation is not requisite for induction of cystatin S gene expression by IPR in developing SMG. However, sympathetic innervation is required for the full IPR response of the cystatin S gene in these glands. Collectively, these experiments suggest that factor(s) derived from the sympathetic nervous system participate in IPR-induced expression of the cystatin S gene in the rat SMG.