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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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 languageEnglish (US)
Pages (from-to)77-82
Number of pages6
Issue number1
StatePublished - Jan 2012


  • Contractility
  • Heart
  • ICA cell
  • δ-Opioid receptor

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience


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