OPIOID PEPTIDE GENE-EXPRESSION IN THE MYOCARDIAL-CELL

Both kappa and delta opioid receptors have been identified in the myoc ardial cell. These receptors ave coupled to phosphoinositide turnover and protein kinase C (PKC) activation and their stimulation affects th e cytosolic Ca2+ and pH homeostasis as well as the contractility and t he myofilament responsiveness to Ca2+. Both the proenkephalin and the prodynorphin gene are expressed in cardiac myocytes. These cells ave a lso able to synthetize and secrete dynorphin B, a biologically active end product of the prodynorphin gene binding selectively the kappa opi oid receptor. Prodynorphin mRNA and dynorphin B expression are markedl y increased in ventricular myocytes isolated from Syrian cardiomyopath ic hamsters (the hypertrophic BIO 14.6 strain), as compared with norma l cells. Nuclear PKC activation and intracellular Ca2+ overload have b een shown to act as the two major signaling mechanisms involved in the increase in prodynorphin gene transcription observed in cardiomyopath ic myocytes. In these cells, secreted dynorphin B activates kappa opio id receptors at the cell surface and elicits an autocrine loop, leadin g to an increase in nuclear PKC activity and to a tonic feed forward s timulation of prodynorphin gene transcription. The possibility that op ioid genes may act in an autocrine fashion to affect myocardial Ca2+ h omeostasis, growth, and differentiation is also discussed. (C) 1998, E lsevier Science Inc.