Cardioprotection with κ-opioid receptor stimulation is associated with a slowing of cross-bridge cycling

W. G. Pyle, T. D. Smith, Polly Hofmann

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Abstract

Opioid and α-adrenergic receptor activation protect the heart from ischemic damage. One possible intracellular mechanism to explain this is that an improvement in ATP availability contributes to cardioprotection. We tested this hypothesis by correlating postischemic left ventricular developed pressure (LVDP) and myofibrillar Ca 2+ -dependent actomyosin Mg 2+ -ATPase from isolated rat hearts treated with the κ-opioid receptor agonist U-50488H (1 μM) or the α-adrenergic receptor agonist phenylephrine (10 μM) + propranolol (3 μM). Preischemic treatment with U-50488H or phenylephrine + propranolol improved postischemic LVDP recovery by 25-30% over control hearts. Ca 2+ -dependent actomyosin Mg 2+ -ATPase was found to be 20% lower in both U-50488H- and phenylephrine + propranolol-treated hearts compared with control hearts. The κ-opioid receptor antagonist nor-binaltorphimine (1 μM) abolished the effects of U-50488H on postischemic LVDP and actomyosin Mg 2+ -ATPase activity. Reduced actomyosin ATP utilization was also suggested in single ventricular myocytes treated with either U-50488H or the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), because U-50488H and PMA lowered maximum velocity of unloaded shortening by 15-25% in myocytes. U-50488H and phenylephrine + propranolol treatment both resulted in increased phosphorylation of troponin I and C protein. These findings are consistent with the hypothesis that κ-opioid and α-adrenergic receptors decrease actin-myosin cycling rate, leading to a conservation of ATP and cardioprotection during ischemia.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number4 48-4
StatePublished - Dec 7 2000

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(trans)-Isomer 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide
Opioid Receptors
Actomyosin
Phenylephrine
Propranolol
Ventricular Pressure
Adenosine Triphosphatases
Adenosine Triphosphate
Adrenergic Receptors
Muscle Cells
Acetates
Troponin C
Adrenergic Agonists
Troponin I
Narcotic Antagonists
Myosins
Protein Kinase C
Actins
Ischemia
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Cardioprotection with κ-opioid receptor stimulation is associated with a slowing of cross-bridge cycling",
abstract = "Opioid and α-adrenergic receptor activation protect the heart from ischemic damage. One possible intracellular mechanism to explain this is that an improvement in ATP availability contributes to cardioprotection. We tested this hypothesis by correlating postischemic left ventricular developed pressure (LVDP) and myofibrillar Ca 2+ -dependent actomyosin Mg 2+ -ATPase from isolated rat hearts treated with the κ-opioid receptor agonist U-50488H (1 μM) or the α-adrenergic receptor agonist phenylephrine (10 μM) + propranolol (3 μM). Preischemic treatment with U-50488H or phenylephrine + propranolol improved postischemic LVDP recovery by 25-30{\%} over control hearts. Ca 2+ -dependent actomyosin Mg 2+ -ATPase was found to be 20{\%} lower in both U-50488H- and phenylephrine + propranolol-treated hearts compared with control hearts. The κ-opioid receptor antagonist nor-binaltorphimine (1 μM) abolished the effects of U-50488H on postischemic LVDP and actomyosin Mg 2+ -ATPase activity. Reduced actomyosin ATP utilization was also suggested in single ventricular myocytes treated with either U-50488H or the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), because U-50488H and PMA lowered maximum velocity of unloaded shortening by 15-25{\%} in myocytes. U-50488H and phenylephrine + propranolol treatment both resulted in increased phosphorylation of troponin I and C protein. These findings are consistent with the hypothesis that κ-opioid and α-adrenergic receptors decrease actin-myosin cycling rate, leading to a conservation of ATP and cardioprotection during ischemia.",
author = "Pyle, {W. G.} and Smith, {T. D.} and Polly Hofmann",
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AU - Pyle, W. G.

AU - Smith, T. D.

AU - Hofmann, Polly

PY - 2000/12/7

Y1 - 2000/12/7

N2 - Opioid and α-adrenergic receptor activation protect the heart from ischemic damage. One possible intracellular mechanism to explain this is that an improvement in ATP availability contributes to cardioprotection. We tested this hypothesis by correlating postischemic left ventricular developed pressure (LVDP) and myofibrillar Ca 2+ -dependent actomyosin Mg 2+ -ATPase from isolated rat hearts treated with the κ-opioid receptor agonist U-50488H (1 μM) or the α-adrenergic receptor agonist phenylephrine (10 μM) + propranolol (3 μM). Preischemic treatment with U-50488H or phenylephrine + propranolol improved postischemic LVDP recovery by 25-30% over control hearts. Ca 2+ -dependent actomyosin Mg 2+ -ATPase was found to be 20% lower in both U-50488H- and phenylephrine + propranolol-treated hearts compared with control hearts. The κ-opioid receptor antagonist nor-binaltorphimine (1 μM) abolished the effects of U-50488H on postischemic LVDP and actomyosin Mg 2+ -ATPase activity. Reduced actomyosin ATP utilization was also suggested in single ventricular myocytes treated with either U-50488H or the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), because U-50488H and PMA lowered maximum velocity of unloaded shortening by 15-25% in myocytes. U-50488H and phenylephrine + propranolol treatment both resulted in increased phosphorylation of troponin I and C protein. These findings are consistent with the hypothesis that κ-opioid and α-adrenergic receptors decrease actin-myosin cycling rate, leading to a conservation of ATP and cardioprotection during ischemia.

AB - Opioid and α-adrenergic receptor activation protect the heart from ischemic damage. One possible intracellular mechanism to explain this is that an improvement in ATP availability contributes to cardioprotection. We tested this hypothesis by correlating postischemic left ventricular developed pressure (LVDP) and myofibrillar Ca 2+ -dependent actomyosin Mg 2+ -ATPase from isolated rat hearts treated with the κ-opioid receptor agonist U-50488H (1 μM) or the α-adrenergic receptor agonist phenylephrine (10 μM) + propranolol (3 μM). Preischemic treatment with U-50488H or phenylephrine + propranolol improved postischemic LVDP recovery by 25-30% over control hearts. Ca 2+ -dependent actomyosin Mg 2+ -ATPase was found to be 20% lower in both U-50488H- and phenylephrine + propranolol-treated hearts compared with control hearts. The κ-opioid receptor antagonist nor-binaltorphimine (1 μM) abolished the effects of U-50488H on postischemic LVDP and actomyosin Mg 2+ -ATPase activity. Reduced actomyosin ATP utilization was also suggested in single ventricular myocytes treated with either U-50488H or the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), because U-50488H and PMA lowered maximum velocity of unloaded shortening by 15-25% in myocytes. U-50488H and phenylephrine + propranolol treatment both resulted in increased phosphorylation of troponin I and C protein. These findings are consistent with the hypothesis that κ-opioid and α-adrenergic receptors decrease actin-myosin cycling rate, leading to a conservation of ATP and cardioprotection during ischemia.

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