title: CCK receptors-related signaling involved in nitric oxide production caused by gastrin 17 in porcine coronary endothelial cells.
abstract: In anesthetized pigs gastrin-17 increased coronary blood flow through CCK1/CCK2 receptors and β(2)-adrenoceptors-related nitric oxide (NO) release. Since the intracellular pathway has not been investigated the purpose of this study was to examine in coronary endothelial cells the CCK1/CCK2 receptors-related signaling involved in the effects of gastrin-17 on NO release. Gastrin-17 caused a concentration-dependent increase of NO production (17.3-62.6%; p<0.05), which was augmented by CCK1/CCK2 receptors agonists (p<0.05). The effect of gastrin-17 was amplified by the adenylyl-cyclase activator and β(2)-adrenoceptors agonist (p<0.05), abolished by cAMP/PKA and β(2)-adrenoceptors and CCK1/CCK2 receptors blockers, and reduced by PLC/PKC inhibitor. Finally, Western-blot revealed the preferential involvement of PKA vs. PKC as downstream effectors of CCK1/CCK2 receptors activation leading to Akt, ERK, p38 and endothelial NOS (eNOS) phosphorylation. In conclusion, in coronary endothelial cells, gastrin-17 induced eNOS-dependent NO production through CCK1/CCK2 receptors- and β(2)-adrenoceptors-related pathway. The intracellular signaling involved a preferential PKA pathway over PKC.
authors.affiliation: Laboratorio di Fisiologia, Dipartimento di Medicina Clinica e Sperimentale, Centro di Biotecnologie per la Ricerca Medica Applicata, Università degli Studi del Piemonte Orientale A. Avogadro, Via Solaroli 17, Chirurgia Sperimentale, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy. grossini@med.unipmn.it
authors.forename: Elena
authors.initials: E
authors.lastname: Grossini
authors.forename: Philippe
authors.initials: P
authors.lastname: Caimmi
authors.forename: Claudio
authors.initials: C
authors.lastname: Molinari
authors.forename: Francesca
authors.initials: F
authors.lastname: Uberti
authors.forename: David
authors.initials: D
authors.lastname: Mary
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vacca
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D005755:Gastrins / Q000494:pharmacology / Q000502:physiology*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology
chemical_list: C090019:8-sulfocholecystokinin octapeptide; D005755:Gastrins; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D011949:Receptors, Cholecystokinin; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; C013550:gastrin 17; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D010418:Pentagastrin; D012844:Sincalide