title: Inhibitory regulation of amylase release in rat parotid acinar cells by benzodiazepine receptors.
abstract: This study examined the influence of benzodiazepine receptors on amylase release from rat parotid acinar cells. Diazepam (10(-8)-10(-6) M), which is a potent agonist of both central- and peripheral-type benzodiazepine receptors, dose dependently decreased amylase release induced by isoprenaline and carbachol, which are beta-adrenoceptor and muscarinic receptor agonists, respectively. The maximum inhibitory response was obtained with 10(-6) M diazepam: amylase release was decreased to 57% (isoprenaline) and 39% (carbachol) of maximal levels, while these responses were completely inhibited by propranolol and atropine, respectively. Clonazepam and 7-chloro-1,3-dihydro-1-methyl-5-p-chlorophenyl)-2H-1,4-benzodiazepine-2- one (Ro 5-4864), which are selective agonists of central- and peripheral-type benzodiazepine receptors, respectively, also produced a significant and dose-dependent decrease in isoprenaline-induced amylase release. The inhibitory potency was diazepam > clonazepam > Ro 5-4864. Flumazenil and 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide (PK 11195), which are selective antagonists of central- and peripheral-type benzodiazepine receptors, respectively, dose dependently blocked the inhibition of isoprenaline-induced amylase release by diazepam. At a concentration of 10(-5) M, flumazenil and PK 11195 restored amylase release to approximately 75% of that in the presence of isoprenaline alone. The combination of both antagonists completely prevented the inhibition by diazepam. Similarly, the inhibitory responses of clonazepam and Ro 5-4864 were completely blocked by flumazenil and PK 11195, respectively. These results suggest that, in rat parotid acinar cells, benzodiazepines inhibit beta-adrenoceptor and muscarinic receptor-stimulated amylase release and that both central- and peripheral-type benzodiazepine receptors contribute to this inhibitory regulation.
authors.affiliation: Department of Pharmacology and Oral Health Science Center, Tokyo Dental College, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okubo
authors.forename: M
authors.initials: M
authors.lastname: Kawaguchi
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000681:Amylases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001570:Benzodiazepinones; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D005442:Flumazenil; D002998:Clonazepam; D001285:Atropine; D002217:Carbachol; D011433:Propranolol; D000681:Amylases; D007545:Isoproterenol; D003975:Diazepam