title: Coupling of β1-adrenergic receptor to type 5 adenylyl cyclase and its physiological relevance in cardiac myocytes.
abstract: 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.
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Takashi
authors: T
authors: Tsunematsu
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Physiology, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan. Electronic address: okumura-s@tsuruni-u.ac.jp.
authors: Satoshi
authors: S
authors: Okumura
authors: Department of Physiology, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan.
authors: Yasumasa
authors: Y
authors: Mototani
authors: Department of Physiology, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan.
authors: Yoshiki
authors: Y
authors: Ohnuki
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Huiling
authors: H
authors: Jin
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Wenqian
authors: W
authors: Cai
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Kenji
authors: K
authors: Suita
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Itaru
authors: I
authors: Sato
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Masanari
authors: M
authors: Umemura
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Utako
authors: U
authors: Yokoyama
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Physiology, Aichi Medical University, Nagakute, 480-1195, Japan.
authors: Motohiko
authors: M
authors: Sato
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Takayuki
authors: T
authors: Fujita
authors: Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: yishikaw@yokohama-cu.ac.jp.
authors: Yoshihiro
authors: Y
authors: Ishikawa
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*
chemical_list: D018342:Receptors, Adrenergic, beta-1; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V
keywords: Adenylyl cyclase; Apoptosis; Cyclic AMP; Heart; β-receptor