This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ebert, S. N. Articles by Thompson, R. P. Search for Related Content PubMed PubMed Citation Articles by Ebert, S. N. Articles by Thompson, R. P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB EPINEPHRINE Related Collections Developmental biology Gene expression Autonomic, reflex, and neurohumoral control of circulation

(Circulation Research. 2001;88:117.)
© 2001 American Heart Association, Inc.

Integrative Physiology

Embryonic Epinephrine Synthesis in the Rat Heart Before Innervation

Association With Pacemaking and Conduction Tissue Development

Steven N. Ebert, Robert P. Thompson

From the Department of Pharmacology, Georgetown University Medical Center (S.N.E.), Washington, DC, and Department of Cell Biology and Anatomy, Medical University of South Carolina (R.P.T.), Charleston, South Carolina.

Correspondence to Steven N. Ebert, PhD, Department of Pharmacology, Georgetown University Medical Center, Medical-Dental Building, SE 402, 3900 Reservoir Rd NW, Washington, DC 20007. E-mail eberts{at}gunet.georgetown.edu

Abstract—Epinephrine is a potent neurotransmitter and hormone that can influence cardiac performance beginning shortly after the first myocardial contractions occur in developing vertebrate embryos. In the present study, we provide evidence that the heart itself may produce epinephrine during embryonic development. Using antibodies that selectively recognize the catecholamine biosynthetic enzymes, tyrosine hydroxylase, dopamine ß-hydroxylase, and phenylethanolamine N-methyltransferase, we used coimmunofluorescent staining techniques to identify cardiac cells that have the capability of producing catecholamines. Initially, cells expressing catecholamine biosynthetic enzymes were found interspersed throughout the myocardium, but by embryonic day 11.5 (E11.5), they became preferentially localized to the dorsal venous valve and atrioventricular canal regions. As development proceeded, catecholamine biosynthetic enzyme expression decreased in these regions but became quite strong along the crest of the interventricular septum by E16.5. This expression pattern was also transient, decreasing in the ventricular septum by E19.5. These data are consistent with a transient and progressive association of catecholamine-producing cells within regions of the heart that become the sinoatrial node, atrioventricular node, and bundle of His. This is the first evidence demonstrating that intrinsic cardiac adrenergic cells may be preferentially associated with early pacemaking and conduction tissue development.

Key Words: phenylethanolamine N-methyltransferase • dopamine ß-hydroxylase • tyrosine hydroxylase • adrenergic

This article has been cited by other articles:

				M.-H. Huang, V. Nguyen, Y. Wu, S. Rastogi, C. Y. Lui, Y. Birnbaum, H.-Q. Wang, D. L. Ware, M. Chauhan, N. Garg, et al. Reducing ischaemia/reperfusion injury through {delta}-opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling Cardiovasc Res, December 1, 2009; 84(3): 452 - 460. [Abstract] [Full Text] [PDF]

				R. Kvetnansky, E. L. Sabban, and M. Palkovits Catecholaminergic Systems in Stress: Structural and Molecular Genetic Approaches Physiol Rev, April 1, 2009; 89(2): 535 - 606. [Abstract] [Full Text] [PDF]

				X. Bao, C. M. Lu, F. Liu, Y. Gu, N. D. Dalton, B.-Q. Zhu, E. Foster, J. Chen, J. S. Karliner, J. Ross Jr, et al. Epinephrine Is Required for Normal Cardiovascular Responses to Stress in the Phenylethanolamine N-Methyltransferase Knockout Mouse Circulation, August 28, 2007; 116(9): 1024 - 1031. [Abstract] [Full Text] [PDF]

				M.-H. Huang, H.-Q. Wang, W. R. Roeske, Y. Birnbaum, Y. Wu, N.-P. Yang, Y. Lin, Y. Ye, D. J. McAdoo, M. G. Hughes, et al. Mediating {delta}-opioid-initiated heart protection via the beta2-adrenergic receptor: role of the intrinsic cardiac adrenergic cell Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H376 - H384. [Abstract] [Full Text] [PDF]

				S. N. Ebert and D. G. Taylor Catecholamines and development of cardiac pacemaking: An intrinsically intimate relationship Cardiovasc Res, December 1, 2006; 72(3): 364 - 374. [Abstract] [Full Text] [PDF]

				M.-H. Huang, J. J. Bahl, Y. Wu, F. Hu, D. F. Larson, W. R. Roeske, and G. A. Ewy Neuroendocrine properties of intrinsic cardiac adrenergic cells in fetal rat heart Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H497 - H503. [Abstract] [Full Text] [PDF]

				A. L. Portbury, R. Chandra, M. Groelle, M. K. McMillian, A. Elias, J. R. Herlong, M. Rios, S. Roffler-Tarlov, and D. M. Chikaraishi Catecholamines act via a beta -adrenergic receptor to maintain fetal heart rate and survival Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2069 - H2077. [Abstract] [Full Text] [PDF]

				X.-K. Liu, A. Katchman, B. H Whitfield, G. Wan, E. M Janowski, R. L Woosley, and S. N Ebert In vivo androgen treatment shortens the QT interval and increases the densities of inward and delayed rectifier potassium currents in orchiectomized male rabbits Cardiovasc Res, January 1, 2003; 57(1): 28 - 36. [Abstract] [Full Text] [PDF]