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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Actin Cytoskeleton, Adrenergic Agents, Animals, Calcium-Binding Proteins, Cardiotonic Agents, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Dogs, Heart, Imidazoles, Isoquinolines, Muscle Relaxation, Myocardial Contraction, Myocardium, Norepinephrine, Phosphorylase Kinase, Phosphorylase a, Phosphorylase b, Phosphorylation, Protein Processing, Post-Translational, Receptors, Adrenergic, beta-1, Receptors, Adrenergic, beta-2, Reserpine, Sarcolemma, Second Messenger Systems, Sulfonamides, Thionucleotides, Troponin C.
user
Is beta2-adrenergic cAMP signaling uncoupled from phosphorylation of cytoplasmic proteins in canine heart? Context: Recent studies of beta-adrenergic receptor (beta-AR) subtype signaling in in vitro preparations have raised doubts as to whether the cAMP/protein kinase A (PKA) signaling is activated in the same manner in response to beta2-AR versus beta1-AR stimulation. The present study compared, in the intact dog, the magnitude and characteristics of chronotropic, inotropic, and lusitropic effects of cAMP accumulation, PKA activation, and PKA-dependent phosphorylation of key effector proteins in response to beta-AR subtype stimulation. In addition, many of these parameters and L-type Ca2+ current (ICa) were also measured in single canine ventricular myocytes. The results indicate that although the cAMP/PKA-dependent phosphorylation cascade activated by beta1-AR stimulation could explain the resultant modulation of cardiac function, substantial beta2-AR-mediated chronotropic, inotropic, and lusitropic responses occurred in the absence of PKA activation and phosphorylation of nonsarcolemmal proteins, including phospholamban, troponin I, C protein, and glycogen phosphorylase kinase. However, in single canine myocytes, we found that beta2-AR-stimulated increases in both ICa and contraction were abolished by PKA inhibition. Thus, the beta2-AR-directed cAMP/PKA signaling modulates sarcolemmal L-type Ca2+ channels but does not regulate PKA-dependent phosphorylation of cytoplasmic proteins.
assistant
These results indicate that the dissociation of beta2-AR signaling from cAMP regulatory systems is only apparent and that beta2-AR-stimulated cAMP/PKA signaling is uncoupled from phosphorylation of nonsarcolemmal regulatory proteins involved in excitation-contraction coupling. Final Decision: yes