title: Effects of calmodulin inhibitors on amylase secretion from rat pancreatic acini.
abstract: To investigate the role of calmodulin in stimulus-secretion coupling in pancreatic acinar cells, we studied the effects of W-7, a calmodulin inhibitor, and KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (Ca2+/CaM kinase II), on amylase secretion from rat pancreatic acini. Calmodulin inhibitor (W-7, 100 microM) and Ca2+/CaM kinase II inhibitor (KN-62, 10 microM) reduced amylase secretion stimulated by cholecystokinin (CCK) or carbachol. W-7 and KN-62 also inhibited amylase secretion stimulated by both calcium ionophore (A23187) and phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA). To clarify the role of calmodulin in the interaction of intracellular mediators, pancreatic acini were permeabilized with streptolysin O. Following permeabilization, amylase secretion was stimulated by submicromolar free Ca2+, and this Ca(2+)-dependent amylase secretion was enhanced by guanosine 5'-[gamma-thio]triphosphate (GTP gamma S), TPA or cyclic adenosine 3',5'-monophosphate (cAMP). W-7 and KN-62 had no effects on amylase secretion stimulated by Ca2+ alone, but inhibited the enhancement in Ca(2+)-dependent amylase secretion by GTP gamma S, TPA or cAMP. These data suggest that calmodulin plays an important role in Ca(2+)-dependent amylase secretion from pancreatic acinar cells and in the interaction between Ca2+ and other intracellular messengers.
authors.affiliation: Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishiguro
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Shibata
authors.forename: M
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Sakai
authors.forename: H
authors.initials: H
authors.lastname: Sobajima
authors.forename: Y
authors.initials: Y
authors.lastname: Nakae
authors.forename: M
authors.initials: M
authors.lastname: Tanikawa
authors.forename: H
authors.initials: H
authors.lastname: Hidaka
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D002147:Calmodulin; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C063302:KN 62; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000681:Amylases; D002118:Calcium