title: Opioid peptide gene expression in the primary hereditary cardiomyopathy of the Syrian hamster. III. Autocrine stimulation of prodynorphin gene expression by dynorphin B.
abstract: Prodynorphin mRNA and dynorphin B expression have been previously shown to be greatly increased in cardiac myocytes of BIO 14.6 cardiomyopathic hamsters. Here we report that exogenous dynorphin B induced a dose-dependent increase in prodynorphin mRNA levels and stimulated prodynorphin gene transcription in normal hamster myocytes. Similar responses were elicited by the synthetic selective kappa opioid receptor agonist U-50,488H. These effects were counteracted by the kappa opioid receptor antagonist Mr-1452 and were not observed in the presence of chelerythrine or calphostin C, two specific protein kinase C (PKC) inhibitors. Treatment of cardiomyopathic cells with Mr-1452 significantly decreased both prodynorphin mRNA levels and prodynorphin gene transcription. In control myocytes, dynorphin B induced the translocation of PKC-alpha to the nucleus and increased nuclear PKC activity without affecting the expression of PKC-delta, -epsilon, or -zeta. Acute release of either U-50,488H or dyn B over single normal or cardiomyopathic cells transiently increased the cytosolic Ca2+ concentration. A sustained treatment with each opioid agonist increased the cytosolic Ca2+ level for a more prolonged period in cardiomyopathic than in control myocytes and led to a depletion of Ca2+ from the sarcoplasmic reticulum in both groups of cells. The possibility that prodynorphin gene expression may affect the function of the cardiomyopathic cell through an autocrine mechanism is discussed.
authors.affiliation: Institute of Biological Chemistry "A. Bonsignore," School of Medicine, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ventura
authors.forename: G
authors.initials: G
authors.lastname: Pintus
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002451:Cell Compartmentation / Q000187:drug effects; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004399:Dynorphins / Q000502:physiology*; D004723:Endorphins / Q000502:physiology*; D004745:Enkephalins / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics*; D011759:Pyrrolidines / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D004723:Endorphins; D004745:Enkephalins; D004791:Enzyme Inhibitors; D011498:Protein Precursors; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D012433:Ryanodine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; C036200:rimorphin; C033660:preproenkephalin; D011493:Protein Kinase C; D002118:Calcium