Altered Responses to Agonists after Chronic In Vivo Atropine Administration in Rat Parotid Acini

Abstract

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 (pHj) 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+], (>2 min). The generation of inositol trisphosphates and inositol tetrakisphosphates after 30 s of muscarinic stimulation was not significantly altered. The resting Clcontent, as well as the stimulated Cl-loss, were reduced in parotid acini after chronic atropine administration. In addition, the muscarinicand a-adrenergic-induced intracellular acidification was blunted, suggesting that reduced HCO3efflux 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+] 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.KEY WORDS: a-adrenergic, muscarinic, intracellular pH, inositol phosphate metabolism, free Ca2+ concentration, exocrine gland.

Characterization of the Calcium Signaling System in the Submandibular Cell Line SMG‐C6

“…In freshly isolated SMG acinar cells, α 1 ‐receptors may not play a critical role in regulating the Ca 2+ signal. It has been reported that parotid gland (PG) acinar cells respond strongly to α 1 ‐agonists, manifesting large increases in IP 3 formation and Ca 2+ mobilization (32, 33), although Soltoff etal . (34) observed that stimulation of rat PG acinar cells with 10 μ M phenylephrine only slightly (35%) increased [Ca 2+ ] i .…”