Adenylyl Cyclase Signaling in the Developing Chick Heart: The Deranging Effect of Antiarrhythmic Drugs
Abstrakt
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 beta-blocking agents on this system.
Application of metoprolol and carvedilol, two commonly used beta-blockers, at embryonic day (ED) 8 significantly downregulated (by about 40%) expression levels of AC5, the dominant cardiac AC isoform, and the amount of Gs alpha 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 Gi alpha protein. These data indicate that beta-blocking agents can strongly derange AC signaling during the first half of embryonic heart development.