Coupling of β1-adrenergic receptor to type 5 adenylyl cyclase and its physiological relevance in cardiac myocytes.
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.
['Tsunematsu|Takashi|T|', 'Okumura|Satoshi|S|', 'Mototani|Yasumasa|Y|', 'Ohnuki|Yoshiki|Y|', 'Jin|Huiling|H|', 'Cai|Wenqian|W|', 'Suita|Kenji|K|', 'Sato|Itaru|I|', 'Umemura|Masanari|M|', 'Yokoyama|Utako|U|', 'Sato|Motohiko|M|', 'Fujita|Takayuki|T|', 'Ishikawa|Yoshihiro|Y|']
D000262:Adenylyl Cyclases D000818:Animals D017209:Apoptosis D002478:Cells, Cultured D000242:Cyclic AMP D051379:Mice D018345:Mice, Knockout D032383:Myocytes, Cardiac D018342:Receptors, Adrenergic, beta-1
Adenylyl cyclase Apoptosis Heart Cyclic AMP β-receptor