TY - JOUR
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
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 - δ-Opioid receptor
KW - Contractility
KW - Heart
KW - ICA cell
UR - http://www.scopus.com/inward/record.url?scp=84855803092&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855803092&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2011.11.010
DO - 10.1016/j.peptides.2011.11.010
M3 - Article
C2 - 22108711
AN - SCOPUS:84855803092
SN - 0196-9781
VL - 33
SP - 77
EP - 82
JO - Peptides
JF - Peptides
IS - 1
ER -