title: Opioid Peptide gene expression in the myocardial cell.
abstract: Both κ and δ opioid receptors have been identified in the myocardial cell. These receptors are coupled to phosphoinositide turnover and protein kinase C (PKC) activation, and their stimulation affects the cytosolic Ca(2+) and pH homeostasis as well as the contractility and the myofilament responsiveness to Ca(2+). Both the proenkephalin and the prodynorphin gene are expressed in cardiac myocytes. These cells are also able to synthetize and secrete dynorphin B, a biologically active end product of the prodynorphin gene binding selectively the κ opioid receptor. Prodynorphin mRNA and dynorphin B expression are markedly increased in ventricular myocytes isolated from Syrian cardiomyopathic hamsters (the hypertrophic BIO 14.6 strain), as compared with normal cells. Nuclear PKC activation and intracellular Ca(2+) overload have been shown to act as the two major signaling mechanisms involved in the increase in prodynorphin gene transcription observed in cardiomyopathic myocytes. In these cells, secreted dynorphin B activates κ opioid receptors at the cell surface and elicits an autocrine loop, leading to an increase in nuclear PKC activity and to a tonic feed-forward stimulation of prodynorphin gene transcription. The possibility that opioid genes may act in an autocrine fashion to affect myocardial Ca(2+) homeostasis, growth, and differentiation is also discussed.
authors.affiliation: Department of Biomedical Sciences, Division of Biochemistry, Laboratory of Cardiovascular Research, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy; National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ventura
authors.forename: G
authors.initials: G
authors.lastname: Pintus
authors.forename: B
authors.initials: B
authors.lastname: Tadolini