Nuclear opioid receptors activate opioid peptide gene transcription in isolated myocardial nuclei.
Opioid-binding sites were identified in highly purified nuclei isolated from hamster ventricular myocardial cells. A significant increase in the maximal binding capacity for a kappa opioid receptor ligand was observed in myocardial nuclei from BIO 14.6 cardiomyopathic hamsters, as compared with nuclei obtained from normal myocytes of the F1B strain. The exposure of isolated nuclei to dynorphin B, a natural agonist of kappa opioid receptors, markedly increased opioid peptide gene transcription. The transcriptional effect was mediated by nuclear protein kinase C activation and occurred at a higher rate in nuclei from cardiomyopathic myocytes than in nuclei isolated from normal cells. Thus, a nuclear endorphinergic system may play an intracrine role in the regulation of gene transcription under both normal and pathological conditions.
Ventura
C
C
Department of Biomedical Sciences, Division of Biochemistry, Laboratory of Cardiovascular Research, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
Maioli
M
M
Pintus
G
G
Posadino
A M
AM
Tadolini
B
B
D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism; D006224:Cricetinae; D004745:Enkephalins / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D018847:Opioid Peptides / Q000235:genetics*; D011493:Protein Kinase C / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D004745:Enkephalins; D018847:Opioid Peptides; D011498:Protein Precursors; D018160:Receptors, Cytoplasmic and Nuclear; D017473:Receptors, Opioid, kappa; C033660:preproenkephalin; D011493:Protein Kinase C