Effects of κ-opioid receptor activation on myocardium

W. G. Pyle, J. W. Lester, Polly Hofmann

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

κ-Opioid receptor stimulation of the heart transiently increases twitch amplitude and decreases Ca 2+ -dependent actomyosin Mg 2+ -ATPase activity through an undetermined mechanism. One purpose of the present study was to determine if the increase in twitch amplitude is due to changes in myofilament Ca 2+ sensitivity. We also wanted to determine if κ-opioid receptor activation alters maximum actin-myosin ATPase activity and Ca 2+ sensitivity of tension in a way consistent with protein kinase A or protein kinase C (PKC) action. Rat hearts were treated with U50,488H (a κ-opioid receptor agonist), phenylephrine plus propranolol (α-adrenergic receptor stimulation), isoproterenol (a β-adrenergic receptor agonist), or phorbol 12-myristate 13-acetate (PMA, receptor independent activator of PKC) or were untreated (control), and myofibrils were isolated. U50,488H, phenylephrine plus propranolol, and PMA all decreased maximum Ca 2+ -dependent actomyosin Mg 2+ -ATPase activity, whereas isoproterenol treatment increased maximum Ca 2+ -dependent actomyosin Mg 2+ -ATPase activity. Untreated myofibrils exposed to exogenous PKC-ε, but not PKC-δ, decreased maximum actomyosin Mg 2+ -ATPase activity. Langendorff-perfused hearts treated with U50,488H, phenylephrine plus propranolol, or isoproterenol had significantly higher ventricular ATP levels compared with control hearts. PKC inhibitors abolished the effects of U50,488H on Ca 2+ -dependent actomyosin Mg 2+ ATPase activity and myocardial ATP levels. U50,488H and PMA treatment of isolated ventricular myocytes increased Ca 2+ sensitivity of isometric tension compared with control myocytes at pH 7.0. The U50,488H-dependent increase in Ca 2+ sensitivity of tension was retained at pH 6.6. Together, these findings are consistent with the hypotheses that 1) the positive inotropy associated with κ-opioid receptor activation may be due in part to a PKC-mediated increase in myofilament Ca 2+ -sensitivity of tension and 2) the κ-opioid receptor-PKC pathway is a modulator of myocardial energy status through reduction of actomyosin ATP consumption.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number2 50-2
StatePublished - Aug 29 2001

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Actomyosin
Opioid Receptors
Protein Kinase C
Myocardium
Myofibrils
Adenosine Triphosphatases
Phenylephrine
Isoproterenol
Propranolol
Adenosine Triphosphate
Muscle Cells
Adrenergic Agonists
Protein C Inhibitor
Myosins
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Adrenergic Receptors
Actins
Acetates

All Science Journal Classification (ASJC) codes

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

Cite this

Effects of κ-opioid receptor activation on myocardium. / Pyle, W. G.; Lester, J. W.; Hofmann, Polly.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 281, No. 2 50-2, 29.08.2001.

Research output: Contribution to journalArticle

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