Dynorphin uses a non-opioid mechanism to potentiate N-methyl-D-aspartate currents in single rat periaqueductal gray neurons.

The interaction of the endogenous K-opioid, dynorphin, with N-methyl-D-aspartate (NMDA) receptors was studied in single periaqueductal gray (PAG) cells using the whole cell patch recording technique. We have found that dynorphin A (1-17) rapidly and reversibly potentiates NMDA-activated currents in a subpopulation of PAG cells. The potentiation cannot be blocked by the non-specific opioid antagonist, naloxone, nor can it be reversed by the specific kappa-opioid antagonist, nor-BNI. In addition, the non-opioid fragment of dynorphin, dynorphin A (2-17), is effective in potentiating NMDA currents, while the specific kappa-opioid, U50,488, cannot mimic the action of dynorphin A (1-17). The non-opioid dynorphin action and the rapid onset and recovery of the potentiation are consistent with the idea that dynorphin interacts directly with NMDA receptors in PAG cells.