title: Effects of calcium-channel blockers on cytosolic free calcium and amylase secretion in rat pancreatic acini.
abstract: We investigated the effects of verapamil and diltiazem on cytosolic free calcium and amylase secretion in rat pancreatic acini. Verapamil and diltiazem reduced a rise in cytosolic free calcium and amylase release stimulated by the maximal concentration (10(-5) M) of carbachol in a dose-dependent manner. High concentrations (500 microM) of verapamil and diltiazem inhibited both the initial and the sustained amylase secretion stimulated by 10(-5) M carbachol. However, at low concentration (1 microM), they showed no effect on amylase secretion by 10(-5) M carbachol. These calcium-channel blockers did not affect calcium mobilization and amylase secretion stimulated by either caerulein or neuromedin C. Binding of 3H-N-methylscopolamine to pancreatic acini was inhibited by verapamil and diltiazem in a dose-dependent manner. These findings suggested that verapamil and diltiazem reduced carbachol-induced amylase secretion probably not due to their calcium-channel blocking activities but due to their non-competitive effects on the level of muscarinic receptors.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Arita
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Yazu
authors.forename: Y
authors.initials: Y
authors.lastname: Ogami
authors.forename: H
authors.initials: H
authors.lastname: Nawata
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019832:N-Methylscopolamine; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012602:Scopolamine Derivatives / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D010446:Peptide Fragments; D012602:Scopolamine Derivatives; C040794:neuromedin C; D002108:Ceruletide; D002217:Carbachol; D014700:Verapamil; D000681:Amylases; D004110:Diltiazem; D001839:Bombesin; D002118:Calcium; D019832:N-Methylscopolamine