Calcium antagonists cause dry mouth by inhibiting resting saliva secretion

Ca2+ antagonists cause dry mouth by inhibiting saliva secretion. The present study was undertaken to elucidate the mechanism by which Ca2+ antagonists cause dry mouth. Since the intracellular Ca2+ concentration ([Ca2+]i) is closely related to saliva secretion, [Ca2+]i was measured with a video-imaging analysis system by using human submandibular gland (HSG) cells as the material. The Ca2+ antagonist, nifedipine, inhibited the elevation in [Ca2+]i induced by 1–10 μM carbachol (CCh), but had no inhibitory effect on that induced by 30 and 100 μM CCh. The other kinds of Ca2+ antagonists, verapamil (10 μM), diltiazem (10 μM), and the inorganic Ca2+ channel blocker, CdCl2 (50 μM), also inhibited the [Ca2+]i elevation induced by 10 μM CCh. The Ca2+ channel activator, Bay K 8644 (5 μM), significantly enhanced the CCh (10 μM)-induced [Ca2+]i elevation. Endothelin-1 and norepinephrine also increased the CCh (10 μM)-induced [Ca2+]i elevation. SKF-96365 reversed the enhancement of the CCh (10 μM)-induced [Ca2+]i elevation caused by AlF4− and phenylephrine. The phospholipase Cβ (PLCβ) inhibitor, U-73122 (5 μM), significantly inhibited the [Ca2+]i elevation induced by 100 μM CCh compared with that induced by 10 μM CCh, while the PLCβ activator, m-3M3FBS (20 μM), significantly increased the [Ca2+]i elevation induced by 100 μM CCh compared with that induced by 10 μM CCh. We therefore conclude that non-selective cation and voltage-dependent Ca2+ channels are involved in resting salivation and that Ca2+ antagonists depress H2O secretion by blocking the Ca2+ channels and thereby cause dry mouth.