Effect of sympathectomy on isoproterenol-induced expression of the cysteine proteinase inhibitor gene, cystatin S, in rat submandibular glands

The autonomic nervous system regulates the secretory function of salivary glands. The volume, rate of secretion and composition of saliva are regulated by both sympathetic (alpha(1)-, alpha(2) and beta(1)-adrenergic) and parasympathetic (muscarinic and cholinergic) receptor systems. The rat cystatin S gene, a member of family 2 of the cysteine proteinase inhibitor superfamily, has a very defined pattern of expression during the postnatal development of the rat submandibular gland. Its expression is not detected in the fetus or in rats up to three weeks of age. After this time, the amount of cystatin S mRNA increases, reaching a conspicuously high concentration at 28 days, and then it declines to a barely detectable level at 32 days of age; cystatin S mRNA is not delectable in the glands of adult animals. However, the beta-adrenoreceptor agonist isoproterenol (LPR) induces high concentrations of cystatin S mRNA in the submandibular gland in vivo. This paper reports experiments analysing the participation of the sympathetic nervous system in the IPR-induced expression of the cystatin S gene. Sympathetic denervation (unilateral and bilateral) by removing the superior cervical ganglion 14 days before a single injection of IPR reduced the expression of the cystatin S gene. Chemical denervation by reserpine (a drug that depletes neurotransmitters in sympathetic nerve terminals) also reduced IPR-induced expression of the gene. Morphological analyses of sympathectomized and reserpine-treated glands showed that the structure of the gland was similar to that of glands of intact animals and to those not treated with reserpine. The hypertrophic response to IPR was less obvious in the sympathectomized glands, but was similar in reserpine treated animals. Collectively, these data suggest that even in the presence of a functional beta(1)-adrenergic receptor pathway, factor(s) from the sympathetic nervous system may be required for IPR-induced expression of the cystatin S gene. (C) 1997 Elsevier Science Ltd.