Delta-opioid augments cardiac contraction through β-adrenergic and CGRP-receptor co-signaling

Vince T. Nguyen; Yewen Wu; Ashley N. Guillory; Bradley K. McConnell; Kenichi Fujise; Ming He Huang

doi:10.1016/j.peptides.2011.11.010

Delta-opioid augments cardiac contraction through β-adrenergic and CGRP-receptor co-signaling

Vince T. Nguyen, Yewen Wu, Ashley N. Guillory, Bradley K. McConnell, Kenichi Fujise, Ming He Huang

Internal Medicine

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13 Scopus citations

Abstract

Cardiac epinephrine and calcitonin gene-related peptide (CGRP) are produced by intrinsic cardiac adrenergic cells (ICA cells) residing in human and animal hearts. ICA cells are neuroparicine cells expressing δ-opioid receptors (DOR). We hypothesized that δ-opioid stimulation of ICA cells enhances epinephrine and CGRP release, which results in the augmentation of heart contraction. Rats were injected with DOR-agonist DPDPE (100 μg/kg) with or without 10-min pretreatment with either β-adrenergic receptor (β-AR) blocker propranolol (2 mg/kg) or CGRP-receptor (CGRPR) blocker CGRP _8-37 (300 μg/kg), or their combination. Hemodynamics were monitored with echocardiogram and systolic blood pressure (SBP) was monitored via a tail arterial catheter. Changes in left ventricular fraction-shortening (LVFS) and heart rate (HR) were observed at 5-min after DPDPE infusion. At 5-min DPDPE induced a 36 ± 18% (p < 0.001) increase of the LVFS, which continues to increase to 51 ± 24% (p < 0.0001) by 10 min, and 68 ± 19% (p < 0.001) by 20 min. The increase in LVFS was accompanied by the decrease of HR by 9 ± 5% (p < 0.01) by 5 min and 11 ± 6% (p < 0.001) by 15 min post DPDPE infusion. This magnitude of HR reduction was observed for the remainder of the 20 min. Despite the HR-reduction, cardiac output was increased by 17 ± 8% (p < 0.05) and 28 ± 5% (p < 0.001) by 5- and 20-min post DPDPE administration, respectively. There was a modest (9 ± 9%, p = 0.03) decrease in SBP that was not apparent until 20 min post DPDPE infusion. The positive inotropism of DPDPE was abrogated in animals pretreated with propranolol, CGRP _8-37, or combined propranolol + CGRP _8-37. Furthermore, in whole animal and cardiomyocyte cell culture preparations, DPDPE induced myocardial protein-kinase A (PKA) activation which was abrogated in the animals pretreated with propranolol + CGRP _8-37. DOR agonists augment myocardial contraction through enhanced β-AR and CGRPR co-signaling.

Original language	English (US)
Pages (from-to)	77-82
Number of pages	6
Journal	Peptides
Volume	33
Issue number	1
DOIs	https://doi.org/10.1016/j.peptides.2011.11.010
State	Published - Jan 2012

Keywords

Contractility
Heart
ICA cell
δ-Opioid receptor

ASJC Scopus subject areas

Biochemistry
Physiology
Endocrinology
Cellular and Molecular Neuroscience

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10.1016/j.peptides.2011.11.010

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@article{ae87dcab51014f458eeedd80e0de5855,

title = "Delta-opioid augments cardiac contraction through β-adrenergic and CGRP-receptor co-signaling",

abstract = "Cardiac epinephrine and calcitonin gene-related peptide (CGRP) are produced by intrinsic cardiac adrenergic cells (ICA cells) residing in human and animal hearts. ICA cells are neuroparicine cells expressing δ-opioid receptors (DOR). We hypothesized that δ-opioid stimulation of ICA cells enhances epinephrine and CGRP release, which results in the augmentation of heart contraction. Rats were injected with DOR-agonist DPDPE (100 μg/kg) with or without 10-min pretreatment with either β-adrenergic receptor (β-AR) blocker propranolol (2 mg/kg) or CGRP-receptor (CGRPR) blocker CGRP 8-37 (300 μg/kg), or their combination. Hemodynamics were monitored with echocardiogram and systolic blood pressure (SBP) was monitored via a tail arterial catheter. Changes in left ventricular fraction-shortening (LVFS) and heart rate (HR) were observed at 5-min after DPDPE infusion. At 5-min DPDPE induced a 36 ± 18% (p < 0.001) increase of the LVFS, which continues to increase to 51 ± 24% (p < 0.0001) by 10 min, and 68 ± 19% (p < 0.001) by 20 min. The increase in LVFS was accompanied by the decrease of HR by 9 ± 5% (p < 0.01) by 5 min and 11 ± 6% (p < 0.001) by 15 min post DPDPE infusion. This magnitude of HR reduction was observed for the remainder of the 20 min. Despite the HR-reduction, cardiac output was increased by 17 ± 8% (p < 0.05) and 28 ± 5% (p < 0.001) by 5- and 20-min post DPDPE administration, respectively. There was a modest (9 ± 9%, p = 0.03) decrease in SBP that was not apparent until 20 min post DPDPE infusion. The positive inotropism of DPDPE was abrogated in animals pretreated with propranolol, CGRP 8-37, or combined propranolol + CGRP 8-37. Furthermore, in whole animal and cardiomyocyte cell culture preparations, DPDPE induced myocardial protein-kinase A (PKA) activation which was abrogated in the animals pretreated with propranolol + CGRP 8-37. DOR agonists augment myocardial contraction through enhanced β-AR and CGRPR co-signaling.",

keywords = "Contractility, Heart, ICA cell, δ-Opioid receptor",

author = "Nguyen, {Vince T.} and Yewen Wu and Guillory, {Ashley N.} and McConnell, {Bradley K.} and Kenichi Fujise and Huang, {Ming He}",

note = "Funding Information: This study was supported by the American Heart Association National Scientist Development Grant (to M.H.) and the National Institute of Health (NIH HL085487 to BKM). ",

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doi = "10.1016/j.peptides.2011.11.010",

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T1 - Delta-opioid augments cardiac contraction through β-adrenergic and CGRP-receptor co-signaling

AU - Nguyen, Vince T.

AU - Wu, Yewen

AU - Guillory, Ashley N.

AU - McConnell, Bradley K.

AU - Fujise, Kenichi

AU - Huang, Ming He

N1 - Funding Information: This study was supported by the American Heart Association National Scientist Development Grant (to M.H.) and the National Institute of Health (NIH HL085487 to BKM).

PY - 2012/1

Y1 - 2012/1

N2 - Cardiac epinephrine and calcitonin gene-related peptide (CGRP) are produced by intrinsic cardiac adrenergic cells (ICA cells) residing in human and animal hearts. ICA cells are neuroparicine cells expressing δ-opioid receptors (DOR). We hypothesized that δ-opioid stimulation of ICA cells enhances epinephrine and CGRP release, which results in the augmentation of heart contraction. Rats were injected with DOR-agonist DPDPE (100 μg/kg) with or without 10-min pretreatment with either β-adrenergic receptor (β-AR) blocker propranolol (2 mg/kg) or CGRP-receptor (CGRPR) blocker CGRP 8-37 (300 μg/kg), or their combination. Hemodynamics were monitored with echocardiogram and systolic blood pressure (SBP) was monitored via a tail arterial catheter. Changes in left ventricular fraction-shortening (LVFS) and heart rate (HR) were observed at 5-min after DPDPE infusion. At 5-min DPDPE induced a 36 ± 18% (p < 0.001) increase of the LVFS, which continues to increase to 51 ± 24% (p < 0.0001) by 10 min, and 68 ± 19% (p < 0.001) by 20 min. The increase in LVFS was accompanied by the decrease of HR by 9 ± 5% (p < 0.01) by 5 min and 11 ± 6% (p < 0.001) by 15 min post DPDPE infusion. This magnitude of HR reduction was observed for the remainder of the 20 min. Despite the HR-reduction, cardiac output was increased by 17 ± 8% (p < 0.05) and 28 ± 5% (p < 0.001) by 5- and 20-min post DPDPE administration, respectively. There was a modest (9 ± 9%, p = 0.03) decrease in SBP that was not apparent until 20 min post DPDPE infusion. The positive inotropism of DPDPE was abrogated in animals pretreated with propranolol, CGRP 8-37, or combined propranolol + CGRP 8-37. Furthermore, in whole animal and cardiomyocyte cell culture preparations, DPDPE induced myocardial protein-kinase A (PKA) activation which was abrogated in the animals pretreated with propranolol + CGRP 8-37. DOR agonists augment myocardial contraction through enhanced β-AR and CGRPR co-signaling.

AB - Cardiac epinephrine and calcitonin gene-related peptide (CGRP) are produced by intrinsic cardiac adrenergic cells (ICA cells) residing in human and animal hearts. ICA cells are neuroparicine cells expressing δ-opioid receptors (DOR). We hypothesized that δ-opioid stimulation of ICA cells enhances epinephrine and CGRP release, which results in the augmentation of heart contraction. Rats were injected with DOR-agonist DPDPE (100 μg/kg) with or without 10-min pretreatment with either β-adrenergic receptor (β-AR) blocker propranolol (2 mg/kg) or CGRP-receptor (CGRPR) blocker CGRP 8-37 (300 μg/kg), or their combination. Hemodynamics were monitored with echocardiogram and systolic blood pressure (SBP) was monitored via a tail arterial catheter. Changes in left ventricular fraction-shortening (LVFS) and heart rate (HR) were observed at 5-min after DPDPE infusion. At 5-min DPDPE induced a 36 ± 18% (p < 0.001) increase of the LVFS, which continues to increase to 51 ± 24% (p < 0.0001) by 10 min, and 68 ± 19% (p < 0.001) by 20 min. The increase in LVFS was accompanied by the decrease of HR by 9 ± 5% (p < 0.01) by 5 min and 11 ± 6% (p < 0.001) by 15 min post DPDPE infusion. This magnitude of HR reduction was observed for the remainder of the 20 min. Despite the HR-reduction, cardiac output was increased by 17 ± 8% (p < 0.05) and 28 ± 5% (p < 0.001) by 5- and 20-min post DPDPE administration, respectively. There was a modest (9 ± 9%, p = 0.03) decrease in SBP that was not apparent until 20 min post DPDPE infusion. The positive inotropism of DPDPE was abrogated in animals pretreated with propranolol, CGRP 8-37, or combined propranolol + CGRP 8-37. Furthermore, in whole animal and cardiomyocyte cell culture preparations, DPDPE induced myocardial protein-kinase A (PKA) activation which was abrogated in the animals pretreated with propranolol + CGRP 8-37. DOR agonists augment myocardial contraction through enhanced β-AR and CGRPR co-signaling.

KW - Contractility

KW - Heart

KW - ICA cell

KW - δ-Opioid receptor

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Delta-opioid augments cardiac contraction through β-adrenergic and CGRP-receptor co-signaling

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Keywords

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