Coupling of β1-adrenergic receptor to type 5 adenylyl cyclase and its physiological relevance in cardiac myocytes. 2015

Takashi Tsunematsu, and Satoshi Okumura, and Yasumasa Mototani, and Yoshiki Ohnuki, and Huiling Jin, and Wenqian Cai, and Kenji Suita, and Itaru Sato, and Masanari Umemura, and Utako Yokoyama, and Motohiko Sato, and Takayuki Fujita, and Yoshihiro Ishikawa
Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

Myocardial β-adrenergic receptor (β-AR) β1- and β2-subtypes are highly homologous, but play opposite roles in cardiac apoptosis and heart failure, as do cardiac adenylyl cyclase (AC) subtypes 5 (AC5) and 6 (AC6): β1-AR and AC5 promote cardiac remodeling, while β2-AR and AC6 activate cell survival pathways. However, the mechanisms involved remain poorly understood. We hypothesized that AC5 is coupled preferentially to β1-AR rather than β2-AR, and we examined this idea by means of pharmacological and genetic approaches. We found that selective inhibition of AC5 with 2'5'-dideoxyadenosine significantly suppressed cAMP accumulation and cardiac apoptosis induced by selective β1-AR stimulation, but had no effect on cAMP accumulation and cardiac apoptosis in response to selective β2-AR stimulation. The results of selective stimulation of β1-AR and β2-AR in neonatal cardiac myocytes prepared from wild-type and AC5-knockout mice were also consistent with the idea that β1-AR selectively couples with AC5. We believe these results are helpful for understanding the mechanisms underlying the different roles of AR subtypes in healthy and diseased hearts.

UI MeSH Term Description Entries
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000262 Adenylyl Cyclases Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP. Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018342 Receptors, Adrenergic, beta-1 A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-1 receptors are equally sensitive to EPINEPHRINE and NOREPINEPHRINE and bind the agonist DOBUTAMINE and the antagonist METOPROLOL with high affinity. They are found in the HEART, juxtaglomerular cells, and in the central and peripheral nervous systems. Adrenergic beta-1 Receptor,Adrenergic beta-1 Receptors,Receptors, beta-1 Adrenergic,beta-1 Adrenergic Receptors,Adrenergic Receptor, beta-1,Receptor, Adrenergic, beta-1,beta 1 Adrenergic Receptor,Adrenergic Receptor, beta 1,Adrenergic Receptors, beta-1,Adrenergic beta 1 Receptor,Adrenergic beta 1 Receptors,Receptor, Adrenergic beta-1,Receptor, beta-1 Adrenergic,Receptors, Adrenergic beta-1,Receptors, beta 1 Adrenergic,beta 1 Adrenergic Receptors,beta-1 Adrenergic Receptor,beta-1 Receptor, Adrenergic,beta-1 Receptors, Adrenergic
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out
D032383 Myocytes, Cardiac Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC). Cardiomyocytes,Muscle Cells, Cardiac,Muscle Cells, Heart,Cardiac Muscle Cell,Cardiac Muscle Cells,Cardiac Myocyte,Cardiac Myocytes,Cardiomyocyte,Cell, Cardiac Muscle,Cell, Heart Muscle,Cells, Cardiac Muscle,Cells, Heart Muscle,Heart Muscle Cell,Heart Muscle Cells,Muscle Cell, Cardiac,Muscle Cell, Heart,Myocyte, Cardiac

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