Prodynorphin-derived peptides

The dynorphin family is composed of multiple peptides generated by posttranslational processing of prodynorphin. They are widely distributed in the central nervous system and occur in peripheral tissues, such as the heart, the gastrointestinal tract, and the adrenal gland. Dynorphin A(l-17) has been widely investigated because it can represent an endogenous ligand for the K-opioid receptor. It displays several biological functions, including the regulation of pain transmission, feeding, and pituitary hormone release, and it may influence myocardial function. C-terminal fragments of dynorphin A(l-17), lacking the N-terminal tyrosine, do not bind to opioid receptors and are excitotoxic by interacting with glutamate receptors. Increased prodynorphin expression, observed in several pathophysiological conditions such as neuropathic pain and heart ischemia, may tilt the balance toward neurotoxic dynorphin derivatives that may contribute to tissue damage. In recent years, implications of dynorphins in drug addiction, neurodegenerative disease, stress and depression have been proved.