title: Modulation of benzodiazepine receptor, adrenoceptor and muscarinic receptor by diazepam in rat parotid gland.
abstract: This study investigated the influence of diazepam on the binding characteristics of adrenoceptor, muscarinic and benzodiazepine receptors in rat parotid gland membrane using a radioligand binding assay. At a concentration of >10(-6)M, diazepam competed with [(3)H]dihydroalprenolol for β-adrenoceptor, but not [(3)H]prazosin for α-adrenoceptor or [(3)H]quinuclidinyl benzilate for muscarinic receptor. Continuous administration of diazepam at doses of 0.4mg/kg/day, i.p. for 7days in rat significantly decreased pilocarpine (4.0mg/kg, i.p.)-induced parotid salivary flow. Diazepam also produced a significant increase in the dissociation constant (Kd) value for [(3)H]dihydroalprenolol binding, but no change in the maximal binding capacity (Bmax) value, and a decrease in the Kd value for [(3)H]diazepam binding to benzodiazepine receptors, but no change in the Kd or Bmax values for [(3)H]prazosin or [(3)H]quinuclidinyl benzilate binding. These results suggest that continuous administration of diazepam modifies affinity for β-adrenoceptor and benzodiazepine receptor binding sites in parotid gland membrane and that changes in these binding sites may be closely related to diazepam-induced suppression of salivary secretion.
authors.affiliation: Department of Pharmacology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ouchi
authors.forename: Hisako
authors.initials: H
authors.lastname: Yamagishi-Wang
authors.forename: Kohei
authors.initials: K
authors.lastname: Sawaki
authors.forename: Masahito
authors.initials: M
authors.lastname: Watanabe
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kawano
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kawaguchi
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
chemical_list: D011941:Receptors, Adrenergic; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D003975:Diazepam