HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/H376    most recent 01195.2006v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Huang, M.-H. Articles by Uretsky, B. F. Search for Related Content PubMed PubMed Citation Articles by Huang, M.-H. Articles by Uretsky, B. F.

Mediating -opioid-initiated heart protection via the ₂-adrenergic receptor: role of the intrinsic cardiac adrenergic cell

¹Department of Internal Medicine, Cardiology Division, ²Research Histopathology Core, ³Department of Neuroscience and Cell Biology, ⁴Department of Surgery, Division of Cardiothoracic Surgery, and ⁵Department of Pathology, University of Texas Medical Branch, Galveston, Texas; and ⁶Department of Medicine, University of Arizona, College of Medicine, Sarver Heart Center, Tucson, Arizona

Submitted 31 October 2006 ; accepted in final form 8 March 2007

Stimulation of cardiac ₂-adrenergic receptor (₂-AR) or -opioid receptor (DOR) exerts a similar degree of cardioprotection against myocardial ischemia in experimental models. We hypothesized that -opioid-initiated cardioprotection is mediated by the intrinsic cardiac adrenergic (ICA) cell via enhanced epinephrine release. Using immunohistochemical and in situ hybridization methods, we detected in situ tyrosine hydroxylase (TH) mRNA and TH immunoreactivity that was colocalized with DOR immunoreactivity in ICA cells in human and rat hearts. Western blot analysis detected DOR protein in ICA cells isolated from rat ventricular myocytes. The physiology of DOR expression was examined by determining changes of cytosolic Ca²⁺ concentration ([Ca²⁺]_i) transients in isolated rat ICA cells using fluorescence spectrophotometry. Exposing the selective -opioid agonist D-[Pen^2,5]enkephalin (DPDPE) to ICA cells increased [Ca²⁺]_i transients in a concentration-dependent manner. Such an effect was abolished by the Ca²⁺ channel blocker nifedipine. HPLC-electrochemical detection demonstrated a 2.4-fold increase in epinephrine release from ICA cells following DPDPE application. The significance of the ICA cell and its epinephrine release in -opioid-initiated cardioprotection was demonstrated in the rat myocardial infarction model and ICA cell-ventricular myocyte coculture. DPDPE administered before coronary artery occlusion or simulated ischemia-reperfusion reduced left ventricular infarct size by 54 ± 15% or myocyte death by 26 ± 4%, respectively. ₂-AR blockade markedly attenuated -opioid-initiated infarct size-limiting effect and abolished -opioid-initiated myocyte survival protection in rat ICA cell-myocyte coculture. Furthermore, -opioid agonist exerted no myocyte survival protection in the absence of cocultured ICA cells during ischemia-reperfusion. We conclude that -opioid-initiated myocardial infarct size reduction is primarily mediated via endogenous epinephrine/₂-AR signaling pathway as a result of ICA cell activation.

-opioid receptor; epinephrine; myocardial ischemia

This article has been cited by other articles:

				S. H. Deo, M. A. Barlow, L. Gonzalez, D. Yoshishige, and J. L. Caffrey Cholinergic location of {delta}-opioid receptors in canine atria and SA node Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H829 - H838. [Abstract] [Full Text] [PDF]