Effects of repeated exposure to isoproterenol in vivo and in vitro on amylase release from rat parotid tissue.

Abstract

Abstract-Effects of repeated exposure to isoproterenol (ISO), in vivo and in vitro, were investigated on amylase release from rat parotid slices responding to secre tagogues. Responses to ISO and dibutyryl cyclic AMP (DBcAMP) were reduced in the tissue from ISO-treated rats (3 mg/kg, 3 times daily for 3 days), but not in the tissue from propranolol plus ISO-treated rats. Administration of inhibitors of protein synthesis with ISO resulted in a protective effect with regard to development of decreased responses to ISO, DBcAMP and carbachol. A decreased response to ISO (10-5 M) was caused by repeated exposure to ISO in vitro and could not be prevented by pretreatment with inhibitors of protein synthesis. Although the basal level of cyclic AMP in parotid tissue was lower in ISO-pretreated rats than in control rats, after incubation with ISO, the level of cyclic AMP did not differ between ISO pretreated and control rats. These results suggest that the decreased response (amylase release) to ISO in the parotid tissue from ISO-pretreated rats may have been due to an impairment of common secretory process(es) involving various secretagogues and that the development of the impairment may be closely con nected to the de novo synthesis of proteins induced by ISO, but not the impairment of the l3-adrenoceptor-adenylate cyclase system.Since it was reported that repeated admin istration of isoproterenol (ISO) in rats caused an enlargement of the salivary glands (1), evidence showing ISO-induced increases of DNA and protein synthesis in these glands has accumulated (2-5). When salivation was stimulated by pilocarpine in rats, the degree of increase in the flow rate of parotid saliva and the concentration of amylase in it were lower in ISO-treated rats than in intact animals (6). Although a similar decrease in the flow rate and protein concen tration of parotid saliva of treated rats was observed after an administration of ISO used as a challenge dose, no significant change was found in concentration of electrolytes in the same saliva (7).It is reported that the number and/or affinity of binding sites for i3-adrenergic agonists in the parotid tissue is decreased by the repeated administration of ISO (8, 9) and, on the other hand, that the increase in cyclic AMP in parotid acinar cells by stimu lation of 3-adrenoceptors may not be es sential for ISO-induced amylase release from these cells (10,11). If the effects of i9 adrenergic and muscarinic agonists on parotid amylase secretion were to decrease concomitantly after repeated treatment with ISO (6, 7), the desensitization of i9 adrenoceptors might be considered to be insufficient to explain the mechanism of the decreased response to a challenge dose of ISO. The present study was undertaken to clarify whether the decreased response to ISO in enlarged parctid glands is mainly due to the impairment of the (9-adrenoceptor adenylate cyclase system. Materials and Methods Animalsand pretreatments: Male Wistar rats weighing 180-200 g were used. These animals were deprived of food 18 hr...

Hypertrophy and Dysfunction of Parotid Gland Induced by Chronic Stimulation of β1-Adrenergic Receptors

“…However, the decreased amylase release was observed in experiments using not only ,3-adrenergic agonists but also other secretagogues, for instance, carbachol and db-cAMP, in the previous study (3). Considering these results, it seems possible that repeated administration of ;3, -adrenergic agonists, in other words, repeated elevation of cAMP concentration, might change the secretory function both structurally and biochemically (3,(22)(23)(24).…”

“…Amylase release from parotid slices: Preparation and incubation of the parotid slices were carried out by the procedure described previously (3). The parotid glands were removed from rats under anesthesia, and pieces of the tissue which together weighed approximately 10 mg were incubated in 5 ml of Krebs-Ringer-Tris solution (pH 7.4) with the following composition (in mM): NaCl, 120; KCI, 15; MgCl2, 1.2; CaCI2, 3.0; Tris (hydroxymethyl)-aminomethane, 20; hydroxy-n-butyric acid, 5.0; bubbled with pure oxygen at 37'.(,'-'.…”

“…Some investigators take interest in this phenomenon as a model of general proliferation and hypertrophy of cells accompanied by DNA synthesis. Recently, we found decreased responses to secre tagogues in amylase release from the tissue slices of hypertrophied parotid glands (3). However, there are many reports as to the presence of subtypes of ;3-adrenergic receptors, the so-called ,31 and ;32-subtypes.…”