title: Mouse embryonic stem cell-derived cardiomyocytes express functional adrenoceptors.
abstract: The cardiogenic capacity of embryonic stem (ES) cells has been well-investigated. However, little is known about the development of adrenoceptor (AR) systems during the process of ES cell differentiation, which are critically important in cardiac physiology and pharmacology. In this present study, we investigated the expression profile of adrenoceptor subtypes, beta-adrenergic modulation of muscarinic receptors and adrenoceptor-related signaling in cardiomyocytes derived from ES cells (ESCMs). Reverse transcription-polymerase chain reaction revealed that undifferentiated mouse ES cells expressed alpha(1A)-, alpha(1B)-, alpha(1D)- and beta(2)-AR mRNA. However, beta(1)-AR was only expressed after vitamin C induction. The expressions of alpha(1A)-, alpha(1D)- and beta(1)-ARs increased significantly while alpha(1B)- and beta(2)-ARs showed no significant change during the differentiation process. Furthermore, we detected the expression of tyrosine hydroxylase. Both alpha(1)-AR and beta-AR could activate extracellular responsive kinase in ESCMs. Isoprenaline could inhibit the expression of M(2) muscarinic receptor protein. CGP20712A, a beta(1)-AR antagonist, up-regulated the expression of M(2) muscarinic receptor while ICI118551, a beta(2)-AR antagonist, showed no effect. These results indicated that functional adrenoceptors and tyrosine hydroxylase, a critical enzyme in catecholamine biosynthesis, were differentially expressed in ESCMs. Adrenoceptor-related signaling pathways and beta-adrenergic modulation of muscarinic receptors were established during differentiation.
authors.affiliation: Department of Cardiology, Peking University Third Hospital, Beijing 100083, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yang
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Kangtao
authors.initials: K
authors.lastname: Ma
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D043585:Receptor, Muscarinic M2 / Q000096:biosynthesis; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis* / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: C547714:Adra1a protein, mouse; C547717:Adra1b protein, mouse; C547720:Adra1d protein, mouse; D007093:Imidazoles; D011412:Propanolamines; D043585:Receptor, Muscarinic M2; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; C026777:ICI 118551; D011433:Propranolol; C049763:CGP 20712A; D014446:Tyrosine 3-Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; D007545:Isoproterenol; D011224:Prazosin