title: Adenylyl cyclase signaling in the developing chick heart: the deranging effect of antiarrhythmic drugs.
abstract: The adenylyl cyclase (AC) signaling system plays a crucial role in the regulation of cardiac contractility. Here we analyzed the key components of myocardial AC signaling in the developing chick embryo and assessed the impact of selected β-blocking agents on this system. Application of metoprolol and carvedilol, two commonly used β-blockers, at embryonic day (ED) 8 significantly downregulated (by about 40%) expression levels of AC5, the dominant cardiac AC isoform, and the amount of Gsα protein at ED9. Activity of AC stimulated by forskolin was also significantly reduced under these conditions. Interestingly, when administered at ED4, these drugs did not produce such profound changes in the myocardial AC signaling system, except for markedly increased expression of Giα protein. These data indicate that β-blocking agents can strongly derange AC signaling during the first half of embryonic heart development.
authors.affiliation: Department of Physiology, Faculty of Science, Charles University in Prague, 128 43 Prague, Czech Republic.
authors.forename: Lucie
authors.identifier: 0000-0002-0629-8798
authors.initials: L
authors.lastname: Hejnova
authors.affiliation: Department of Physiology, Faculty of Science, Charles University in Prague, 128 43 Prague, Czech Republic.
authors.forename: Klara
authors.initials: K
authors.lastname: Hahnova
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Kockova
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Svatunkova
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic ; Institute of Anatomy, First Faculty of Medicine, Charles University in Prague, 128 00 Prague, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Sedmera
authors.affiliation: Department of Physiology, Faculty of Science, Charles University in Prague, 128 43 Prague, Czech Republic.
authors.forename: Jiri
authors.identifier: 0000-0002-6372-0131
authors.initials: J
authors.lastname: Novotny
mesh_terms: D000262:Adenylyl Cyclases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D002227:Carbazoles / Q000008:administration & dosage; D000077261:Carvedilol; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics / Q000254:growth & development*; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000254:growth & development*; D008790:Metoprolol / Q000008:administration & dosage; D009206:Myocardium / Q000201:enzymology; D011412:Propanolamines / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V; D008790:Metoprolol