{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:31:18Z","timestamp":1771633878335,"version":"3.50.1"},"reference-count":31,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p>Previously, we presented in vivo evidence for a physiological significance of cAMP-regulated CFTR Cl<jats:sup>\u2212<\/jats:sup>channels in Ca<jats:sup>2+<\/jats:sup>-activated Cl<jats:sup>\u2212<\/jats:sup>reabsorption in the ductal system of the rat submandibular gland. Here, we address the mechanism by which basal CFTR activation contributes to the transepithelial Cl<jats:sup>\u2212<\/jats:sup>movement evoked by muscarinic stimulation. The Cl<jats:sup>\u2212<\/jats:sup>concentration ([Cl<jats:sup>\u2212<\/jats:sup>]) was increased in the final saliva from rat submandibular gland during pilocarpine stimulation when a small interfering RNA for CFTR or a specific CFTR inhibitor, CFTR<jats:sub>inh<\/jats:sub>-172, was injected retrogradely into the gland's own duct, indicating that basal CFTR activation is involved in Cl<jats:sup>\u2212<\/jats:sup>reabsorption. Systemically administered propranolol failed to alter the [Cl<jats:sup>\u2212<\/jats:sup>], suggesting little involvement of a \u03b2-adrenergic pathway in the Cl<jats:sup>\u2212<\/jats:sup>movement that occurs through basal CFTR activation. Intraductal injection of suramin (a nonspecific P2-receptor antagonist) increased the salivary [Cl<jats:sup>\u2212<\/jats:sup>], indicating the existence of endogenous purinergic activation. Upon separate intraductal injection, ATP and a P2Y<jats:sub>2<\/jats:sub>-receptor agonist, UTP, decreased the salivary [Cl<jats:sup>\u2212<\/jats:sup>] almost equipotently. CFTR<jats:sub>inh<\/jats:sub>-172 and suramin each prevented these effects, whereas 2\u2032,3\u2032- O-(4-benzoylbenzoyl)-ATP (Bz-ATP), a P2X<jats:sub>7<\/jats:sub>agonist, had no specific effect. Pilocarpine stimulation evoked ATP secretion into the salivary fluid. Immunohistochemistry revealed the partial coexistence of CFTR and P2Y<jats:sub>2<\/jats:sub>receptors on the luminal surface of epithelial cells in the striated ducts of this gland. These results raise the possibility that muscarinic stimulation-induced Cl<jats:sup>\u2212<\/jats:sup>reabsorption occurs through basal CFTR activity and that this is regulated by P2Y<jats:sub>2<\/jats:sub>receptors in the ductal epithelium via stimulation by ATP secreted into the salivary fluid.<\/jats:p>","DOI":"10.1152\/ajpregu.00758.2007","type":"journal-article","created":{"date-parts":[[2008,3,13]],"date-time":"2008-03-13T00:35:53Z","timestamp":1205368553000},"page":"R1729-R1736","source":"Crossref","is-referenced-by-count":42,"title":["Involvement of apical P2Y<sub>2<\/sub>receptor-regulated CFTR activity in muscarinic stimulation of Cl<sup>\u2212<\/sup>reabsorption in rat submandibular 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