European Journal of Pharmacology 1998-10-23

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

M Okubo, M Kawaguchi

Index: Eur. J. Pharmacol. 359 , 243-249, (1998)

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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.