The chronically reserpinized rat as a model for cystic fibrosis: alterations in the mucus-secreting sublingual gland.

Abstract

Summary: The chronic administration of reserpine (0.5 mg/kg body weight, daily for 7 days) increases the density of adrenergic receptors in the sublingual gland of the rat. The Bmax values (in pmole/g tissue) were 5.8 ± 0.9 for [3H]-prazosin, 22 ± 4 for [3H]-clonidine and 11.9 ± 1.7 for [3H]-dihydroalpranolol. These radioligands are used, respectively, for the study of α1, α2 and β-adrenergic receptors and the Bmax values indicated are 181, 226, and 331%, respectively, of the corresponding values in control sublingual glands. The increase in the density of α1-adrenregic receptors was accompanied by the development of a clear secretory response to norepinephrine and phenylephrine, as judged by the ability to release K+ in vitro. This response, which was not observed in control sublingual glands, amounted to 21.9 ± 2.5 and 16.8 ± 3.1% of the tissue content of K+, respectively, for the two agonists. Neither the density of muscarinic cholinergic receptors (Bmax = 106% of control value) nor the extent of K+ release elicited by carbamylcholine was modified by the drug treatment, when compared to those observed in control glands. In vivo, the volume of sublingual saliva secreted in response to i.v. infusions of acetylcholine was significantly reduced in the treated animals to 45% of that secreted by control rats. This was accompanied by increases in salivary concentrations of protein-bound carbohydrates, with no change in the individual carbohydrate ratios. No significant changes in salivary electrolyte concentrations (Na+, K+, Ca++) were observed in sublingual saliva of reserpine-treated rats. In summary, reserpine administration alters adrenergic receptor density and sensitivity in the rat sublingual gland and modifies its secretory responses both in vitro and in vivo. The chronic administration of reserpine to rats causes widespread exocrine gland disturbances resembling those of cystic fibrosis. The results of this study show that the drug treatment also affects a mucus-secreting salivary gland and support the view that the reserpine-treated rat is a useful experimental model of the human disease.