Mediating δ-opioid-initiated heart protection via the β2-adrenergic receptor: Role of the intrinsic cardiac adrenergic cell

Ming He Huang, Hui Qun Wang, William R. Roeske, Yochai Birnbaum, Yewen Wu, Ning Ping Yang, Yu Lin, Yumei Ye, David J. McAdoo, Michael G. Hughes, Scott D. Lick, Paul J. Boor, Charles Y. Lui, Barry F. Uretsky

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Stimulation of cardiac β2-adrenergic receptor (β2-AR) or δ-opioid receptor (DOR) exerts a similar degree of cardioprotection against myocardial ischemia in experimental models. We hypothesized that δ-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 δ-opioid agonist D-[Pen2,5]enkephalin (DPDPE) to ICA cells increased [Ca2+]i transients in a concentration-dependent manner. Such an effect was abolished by the Ca 2+ 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 δ-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. β2-AR blockade markedly attenuated δ-opioid-initiated infarct size-limiting effect and abolished δ-opioid-initiated myocyte survival protection in rat ICA cell-myocyte coculture. Furthermore, δ-opioid agonist exerted no myocyte survival protection in the absence of cocultured ICA cells during ischemia-reperfusion. We conclude that δ-opioid-initiated myocardial infarct size reduction is primarily mediated via endogenous epinephrine/β2-AR signaling pathway as a result of ICA cell activation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number1
DOIs
StatePublished - Jul 2007

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Adrenergic Agents
Adrenergic Receptors
Opioid Analgesics
Muscle Cells
D-Penicillamine (2,5)-Enkephalin
Epinephrine
Tyrosine 3-Monooxygenase
Coculture Techniques
Reperfusion
Ischemia
Myocardial Infarction
Enkephalins
Coronary Occlusion
Fluorescence Spectrometry
Opioid Receptors
Nifedipine
In Situ Hybridization
Myocardial Ischemia
Coronary Vessels
Theoretical Models

Keywords

  • δ-opioid receptor
  • Epinephrine
  • Myocardial ischemia

ASJC Scopus subject areas

  • Physiology

Cite this

Mediating δ-opioid-initiated heart protection via the β2-adrenergic receptor : Role of the intrinsic cardiac adrenergic cell. / Huang, Ming He; Wang, Hui Qun; Roeske, William R.; Birnbaum, Yochai; Wu, Yewen; Yang, Ning Ping; Lin, Yu; Ye, Yumei; McAdoo, David J.; Hughes, Michael G.; Lick, Scott D.; Boor, Paul J.; Lui, Charles Y.; Uretsky, Barry F.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 293, No. 1, 07.2007.

Research output: Contribution to journalArticle

Huang, MH, Wang, HQ, Roeske, WR, Birnbaum, Y, Wu, Y, Yang, NP, Lin, Y, Ye, Y, McAdoo, DJ, Hughes, MG, Lick, SD, Boor, PJ, Lui, CY & Uretsky, BF 2007, 'Mediating δ-opioid-initiated heart protection via the β2-adrenergic receptor: Role of the intrinsic cardiac adrenergic cell', American Journal of Physiology - Heart and Circulatory Physiology, vol. 293, no. 1. https://doi.org/10.1152/ajpheart.01195.2006
Huang, Ming He ; Wang, Hui Qun ; Roeske, William R. ; Birnbaum, Yochai ; Wu, Yewen ; Yang, Ning Ping ; Lin, Yu ; Ye, Yumei ; McAdoo, David J. ; Hughes, Michael G. ; Lick, Scott D. ; Boor, Paul J. ; Lui, Charles Y. ; Uretsky, Barry F. / Mediating δ-opioid-initiated heart protection via the β2-adrenergic receptor : Role of the intrinsic cardiac adrenergic cell. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 293, No. 1.
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AU - Birnbaum, Yochai

AU - Wu, Yewen

AU - Yang, Ning Ping

AU - Lin, Yu

AU - Ye, Yumei

AU - McAdoo, David J.

AU - Hughes, Michael G.

AU - Lick, Scott D.

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N2 - Stimulation of cardiac β2-adrenergic receptor (β2-AR) or δ-opioid receptor (DOR) exerts a similar degree of cardioprotection against myocardial ischemia in experimental models. We hypothesized that δ-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 δ-opioid agonist D-[Pen2,5]enkephalin (DPDPE) to ICA cells increased [Ca2+]i transients in a concentration-dependent manner. Such an effect was abolished by the Ca 2+ 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 δ-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. β2-AR blockade markedly attenuated δ-opioid-initiated infarct size-limiting effect and abolished δ-opioid-initiated myocyte survival protection in rat ICA cell-myocyte coculture. Furthermore, δ-opioid agonist exerted no myocyte survival protection in the absence of cocultured ICA cells during ischemia-reperfusion. We conclude that δ-opioid-initiated myocardial infarct size reduction is primarily mediated via endogenous epinephrine/β2-AR signaling pathway as a result of ICA cell activation.

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