title: Rebamipide, an anti-ulcerative drug, inhibits induction of salivary dysfunction by benzodiazepines.
abstract: OBJECTIVE
  The purpose of this study was to determine whether rebamipide, an antistomach ulcer agent, ameliorated benzodiazepine-induced hyposalivation in rat parotid gland (PG) and submandibular gland (SMG).
  
  
  METHODS
  Saliva was collected from PG and SMG through a capillary cannula inserted into the parotid duct and sublingual papillae, respectively, every 15 min for 1 h after stimulation with pilocarpine dissolved in physiological saline and intraperitoneally administered at 1 mg kg-1. Diazepam (DZP) was administered intraperitoneally at a dose of 0.2 mg kg-1twice daily for 7 days. Rebamipide was administered at 10, 20, 30, or 100 mg kg-1concomitantly with DZP to determine its effect on hyposalivation. The effect of rebamipide on movement of intracellular calcium ([Ca2+]i) in isolated parotid acinar cells was analyzed using Fluo4, a fluorescent dye used to detect Ca2+.
  
  
  RESULTS
  Repetitive administration of DZP decreased salivary secretion in PG and SMG. This inhibitory effect was weakened by administration of rebamipide. Prior administration of DZP (10-6M) significantly suppressed carbachol (10-7M)-induced increase in [Ca2+]i. This inhibitory effect was ameliorated by combined use with rebamipide (5 × 10-4M).
  
  
  CONCLUSIONS
  This findings suggest that rebamipide weakens the downregulatory effect of DZP on salivary secretion by preventing DZP-induced suppression of increase in [Ca2+]i.
authors.affiliation: Department of Pharmacology, Tokyo Dental College, Chiyoda-ku, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ogane
authors.affiliation: Department of Pharmacology, Tokyo Dental College, Chiyoda-ku, Japan.
authors.forename: M
authors.identifier: http://orcid.org/0000-0001-7422-0944
authors.initials: M
authors.lastname: Okubo
authors.affiliation: Department of Clinical Pharmacology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: Department of Pharmacology, Tokyo Dental College, Chiyoda-ku, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shinomiya
authors.affiliation: Department of Pharmacology, Tokyo Dental College, Chiyoda-ku, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Tsukagoshi
authors.affiliation: Department of Pharmacology, Tokyo Dental College, Chiyoda-ku, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kawaguchi
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003975:Diazepam / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D015363:Quinolones / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014987:Xerostomia / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D000897:Anti-Ulcer Agents; D002491:Central Nervous System Agents; D015363:Quinolones; C052785:rebamipide; D000409:Alanine; D003975:Diazepam
keywords: diazepam; hyposalivation; rebamipide; salivary secretion; sialogogue