Opioid Receptors and Endorphinergic Systems 2.0

Dear Colleagues,

Different cell populations express selected types of opioid receptors (i.e., m, d and k), being not only a target, but even a source for a number of biologically active end-products of endorphin genes, including for example the prodynorphin and the pro-enkephalin genes. The interaction between these peptides and their related receptors plays a crucial role in signal transduction circuitries. It is now increasingly becoming evident that the activity of endorphinergic systems is fashioned at multiple interconnected levels and it is controlled by a complex interplay between cell signaling, nucleosomal assembly, the establishment of multifaceted transcriptional motifs and the temporal and spatial organization of chromatin into loops and domains. Opioid peptides not only elicit paracrine and autocrine mechanisms of cell regulation, but they have also been found to act intracellularly. It turns out that cell nuclei harbor the potential for intrinsic signal transduction pathway(s). The term intracrine has been proposed for growth regulatory peptides that have been shown to act within their cell of synthesis at the level of the nuclear envelope, chromatin, or other subnuclear components. Consistent evidence links known intracrines with transcriptional responses and self-sustaining loops that behave as long-lived signals imparting features characteristic of cell growth, differentiation and memory. Within this context, we have shown that the prodynorphin gene and its biologically active product dynorphin B act as major conductors of cardiogenesis in both embryonic and adult stem cells, and that dynorphin B can act in an intracrine fashion at the level of nuclear opioid receptors in stem cells, coupling nuclear signaling with the transcription of cardiogenic genes.

Prof. Dr. Carlo Ventura
Guest Editor

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