Inhibitory regulation of amylase release in rat parotid acinar cells by benzodiazepine receptors

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 an 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 similar to 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. (C) 1998 Elsevier Science B.V. All rights reserved.