Salivary gland hypofunction, resulting from a variety of perturbations including prescribed medications, is associated with adverse effects on the health of the oral cavity. In the present study, we investigated the in vivo effects of chronic administration of atropine, a muscarinic antagonist, on the acute response of rat parotid acini to a-adrenergic and muscarinic stimulation. The regulation of intracellular pH (pHi) and cytosolic free Ca2* ([Ca2+]i) were monitored using dual wavelength microfluorometry of the ion-sensitive fluorescent dyes, BCECF and fura-2, respectively. Chronic atropine treatment (40 mg/kg/d for 4 weeks) significantly increased the magnitude of the initial (<30 s) agonist-induced rise in [Ca2+]i, but did not alter the sustained increase in [Ca2+]i (>2 min). The generation of inositol trisphosphates and inositol tetrakisphosphates after 30 s of muscarinic stimulation was not significantly altered. The resting Cl- content, as well as the stimulated Cl- loss, were reduced in parotid acini after chronic atropine administration. In addition, the muscarinic- and a-adrenergic-induced intracellular acidification was blunted, suggesting that reduced HCO3- efflux occurs in acini isolated from atropine-treated animals. Our results indicate (1) that chronic atropine treatment does not inhibit the receptor-coupled generation of inositol phosphates or the resulting rise in [Ca2+]i and (2) chronic treatment may prevent the production of saliva either by reducing the driving force for anion-dependent fluid secretion or by preventing the activation of the anion efflux pathway.
Sodium requirement in secretory processes regulated through muscarinic receptors in rat parotid glands
