Abstract
1. The aims of the present study were to determine whether delta-opioid receptor stimulation enhanced proliferation of and to investigate the role of the extracellular signal-regulated kinase (ERK) pathway in ventricular myocytes from neonatal rats. 2. At concentratins ranging from 10 nmol/L to 10 micromol/L, [D-Ala2,D-Leu5]enkephalin (DADLE) concentration-dependently promoted myocardial growth and DNA synthesis and altered the cytoskeleton. 3. At 1 micromol/L, DADLE also increased the expression and phosphorylation of ERK. 4. These effects of 1 micromol/L DADLE were abolished by 10 micromol/L naltrindole, a selective delta-opioid receptor antagonist, 10 nmol/L U0126, a selective ERK antagonist, 1 micromol/L staurosporine, an inhibitor of protein kinase (PK) C, and 100 micromol/L Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt hydrate (Rp-cAMPS), an inhibitor of PKA. 5. In conclusion, delta-opioid receptor stimulation enhances the proliferation and development of the ventricular myocytes of neonatal rats. The ERK pathway and related signalling mechanisms, namely PKC and PKA, are involved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics, Opioid / pharmacology*
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Animals
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Animals, Newborn
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Butadienes / pharmacology
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Cell Proliferation / drug effects*
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Cells, Cultured
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / pharmacology
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cytoskeleton / drug effects
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Dose-Response Relationship, Drug
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Enkephalin, Leucine-2-Alanine / pharmacology*
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Heart Ventricles / drug effects
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Heart Ventricles / metabolism
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Myocytes, Cardiac / drug effects*
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Myocytes, Cardiac / enzymology
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Myocytes, Cardiac / metabolism
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Naltrexone / analogs & derivatives
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Naltrexone / pharmacology
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Narcotic Antagonists / pharmacology
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Nitriles / pharmacology
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Phosphorylation
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Protein Kinase Inhibitors / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Opioid, delta / agonists*
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Receptors, Opioid, delta / metabolism
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Signal Transduction / drug effects*
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Staurosporine / pharmacology
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Thionucleotides / pharmacology
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Time Factors
Substances
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Analgesics, Opioid
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Butadienes
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Narcotic Antagonists
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Nitriles
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Protein Kinase Inhibitors
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Receptors, Opioid, delta
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Thionucleotides
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U 0126
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adenosine-3',5'-cyclic phosphorothioate
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Naltrexone
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Enkephalin, Leucine-2-Alanine
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Extracellular Signal-Regulated MAP Kinases
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naltrindole
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Staurosporine