title: Diazepam enhances production of diazepam-binding inhibitor (DBI), a negative saliva secretion regulator, localized in rat salivary gland.
abstract: Peripheral-type benzodiazepine receptor (PBR) and central-type benzodiazepine receptor (CBR) in salivary gland play a role in the inhibitory regulation of salivary secretion in rodents. Diazepam-binding inhibitor (DBI), an endogenous ligand for PBR, produces neurosteroids, which modulate CBR activity. In this study, we investigated the effect of repetitive administration of diazepam (DZP) on salivary secretion and expression of DBI mRNA and peptide. Moreover, mRNA expression of PBR and pituitary adenylate cyclase-activating polypeptide (PACAP), a transcriptional regulator for DBI promoter, was evaluated after repetitive administration of DZP. Repetitive administration, but not single administration, of 0.4 mg/kg DZP caused inhibition of salivary secretion and enhanced expression of DBI, PACAP, and PBR mRNA in rat salivary gland, with an increase in production of DBI peptide. These results suggest that repetitive administration of DZP stimulates DBI production, which may result in an increase in the suppressive effect of DZP on salivary secretion.
authors.affiliation: Department of Pharmacology, Tokyo Dental College, Chiba 261-8502, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Tsukagoshi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Shinomiya
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kawano
authors.forename: Migiwa
authors.initials: M
authors.lastname: Okubo
authors.forename: Kohei
authors.initials: K
authors.lastname: Sawaki
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D012463:Saliva / Q000378:metabolism*; D012469:Salivary Glands / Q000187:drug effects* / Q000378:metabolism*; D012472:Salivation / Q000187:drug effects*
chemical_list: D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D003975:Diazepam