title: Calcium antagonists cause dry mouth by inhibiting resting saliva secretion.
abstract: 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 microM carbachol (CCh), but had no inhibitory effect on that induced by 30 and 100 microM CCh. The other kinds of Ca2+ antagonists, verapamil (10 microM), diltiazem (10 microM), and the inorganic Ca2+ channel blocker, CdCl2 (50 microM), also inhibited the [Ca2+]i elevation induced by 10 microM CCh. The Ca2+ channel activator, Bay K 8644 (5 microM), significantly enhanced the CCh (10 microM)-induced [Ca2+]i elevation. Endothelin-1 and norepinephrine also increased the CCh (10 microM)-induced [Ca2+]i elevation. SKF-96365 reversed the enhancement of the CCh (10 microM)-induced [Ca2+]i elevation caused by AlF4- and phenylephrine. The phospholipase Cbeta (PLCbeta) inhibitor, U-73122 (5 microM), significantly inhibited the [Ca2+]i elevation induced by 100 microM CCh compared with that induced by 10 microM CCh, while the PLCbeta activator, m-3M3FBS (20 microM), significantly increased the [Ca2+]i elevation induced by 100 microM CCh compared with that induced by 10 microM 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.
authors: Department of Dental Pharmacology, Matsumoto Dental University, 1780 Hirooka-Gohbara, Shiojiri, Nagano 399-0781, Japan. hattori@po.mdu.ac.jp
authors: Toshimi
authors: T
authors: Hattori
authors: Pao-Li
authors: PL
authors: Wang
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D002217:Carbachol / Q000494:pharmacology; D045744:Cell Line, Tumor; D003864:Depression, Chemical; D019332:Endothelin-1 / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018721:Muscarinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D054799:Phospholipase C beta; D012463:Saliva / Q000378:metabolism*; D013365:Submandibular Gland Neoplasms / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014987:Xerostomia / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D019332:Endothelin-1; D007093:Imidazoles; D007527:Isoenzymes; D018721:Muscarinic Agonists; D014662:Vasoconstrictor Agents; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002217:Carbachol; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium; D009638:Norepinephrine