title: Mediation of pepsinogen secretion from guinea pig chief cells by Ca2+/calmodulin-dependent protein kinase II.
abstract: In the presence of Ca2+ bound to calmodulin, Ca2+/calmodulin-dependent protein kinase II (CaMK II) exhibits an intramolecular autophosphorylation and modulates many cell functions. In this study, the role of CaMK II in pepsinogen secretion was investigated in cultured guinea pig chief cells by using a specific CaMK II inhibitor, 1-[N,O-Bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpipera zin e (KN-62), and an antibody for the Thr-286-autophosphorylated alpha subunit of CaMK II which specifically recognized the autophosphorylated form of CaMK II. KN-62 inhibited the pepsinogen secretion stimulated by carbamylcholine chloride, cholecystokinin octapeptide, and ionomycin in a dose-dependent manner without affecting intracellular Ca2+ concentrations, but had no effect on the secretion by 12-O-tetradecanoyl phorbol-13-acetate (TPA) and forskolin. Heavy staining with the antibody for autophosphorylated CaMK II was observed in the cytoplasm of chief cells treated with carbamylcholine chloride or ionomycin, but only light staining was seen in cells treated with TPA or forskolin. Thus, CaMK II and its autophosphorylation may be a critical step in the intracellular pathway in which Ca2+ causes pepsinogen secretion from guinea pig chief cells.
authors.affiliation: First Department of Internal Medicine, Nagoya City University Medical School, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Okayama
authors.forename: M
authors.initials: M
authors.lastname: Itoh
authors.forename: T
authors.initials: T
authors.lastname: Joh
authors.forename: T
authors.initials: T
authors.lastname: Miyamoto
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Moriyama
authors.forename: T
authors.initials: T
authors.lastname: Kato
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D005753:Gastric Mucosa / Q000378:metabolism*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D015759:Ionomycin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010435:Pepsinogens / Q000378:metabolism*; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; D010435:Pepsinogens; D010879:Piperazines; D015759:Ionomycin; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002217:Carbachol; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases