The dynorphins comprise one of the three families of opioid peptides. They are found throughout the nervous system, they have diverse physiologic functions. They are highly selective for one of the opioid receptor types, the Kappa receptor. We shall carry out five projects -- four of them ongoing now, one of them (#2 below) new. 1. Continue and complete our development of valid type-specific binding assays in order to study the distribution and function of the Kappa receptors, and to guide the testing of new and type-selective opioids with possible therapeutic value. 2. Attempt the cloning of Kappa receptors (in collaboration with a genetic engineering group) in order to learn their primary structure and molecular function. 3. Continue our studies on dynorphin-produced analgesia at the spinal cord level, to learn more about the role of dynorphins in normal pain regulation and in acupuncture analgesia. 4. Purify and further characterize the unique processing enzyme (convertase) that cleaves a precursor peptide specifically to yield dynorphin B. 5. Attempt to demonstrate biosynthesis of the novel morphinelike opiates (including morphine itself) that we have isolated from beef brain and adrenal, the structures of which are presently being determined.
