This issue of Molecular Pharmacology is dedicated to Dr. Avram Goldstein, the journal's founding editor and one of the leaders in the development of modern pharmacology. This article focuses on his contributions to the discovery of the
dynorphins and evidence that members of this family of
opioid peptides are endogenous agonists for the
kappa opioid receptor. In his original publication describing the purification and sequencing of
dynorphin A, Avram described this
peptide as "extraordinarily potent" ("dyn" from the Greek, dynamis = power and "orphin" for endogenous
morphine peptide). The name originally referred to its high affinity and great potency in the bioassay that was used to follow its activity during purification, but the name has come to have a second meaning: studies of its physiologic function in brain continue to provide powerful insights to the molecular mechanisms controlling
mood disorders and
drug addiction. During the 30 years since its discovery, we have learned that the
dynorphin peptides are released in brain during stress exposure. After they are released, they activate
kappa opioid receptors distributed throughout the brain and spinal cord, where they trigger cellular responses resulting in different stress responses:
analgesia, dysphoria-like behaviors, anxiety-like responses, and increased addiction behaviors in experimental animals. Avram predicted that a detailed molecular analysis of
opiate drug actions would someday lead to better treatments for
drug addiction, and he would be gratified to know that subsequent studies enabled by his discovery of the
dynorphins resulted in insights that hold great promise for new treatments for addiction and
depressive disorders.