PROENKEPHALIN A NEUROPEPTIDES IN HUMAN EPILEPTOGENIC TISSUE

We hypothesize that neuropeptides are involved in temporal lobe epilepsy. To elucidate the molecular mechanisms involved in epilepsy, several opioid neuropeptides were measured in surgically removed human temporal lobe cortex. The opioid neuropeptides studied derived from several different precursor molecules, including proenkephalin A, which produces methionine enkephalin (ME=TyrGlyGlyPheMet=YGGFM), leucine enkephalin (LE=TyrGlyGlyPheLeu=YGGFL), and ME-RGL (TyrGlyGlyPheMetArgGlyLeu), and proopiomelanocortin (POMC), which produces beta-endorphin (BE). Opioid neuropeptide receptor activity was measured in tissue obtained from the medial (epileptogenic focus) temporal cortex (MTC) and the lateral (nonfocus) temporal cortex (LTC). The epileptogenic focus was localized previous to surgery by long-term ictal monitoring with surgically implanted subdural strip electrodes. The opioid neuropeptide receptor activity content in the MTC and LTC tissue samples was compared between patients who were seizure-free (OT had auras only) and those who were not seizure-free postoperatively. The methionine enkephalin-like receptor activity (ME-1r) measurements were the only values that showed significant difference. The amount of ME-1r in the MTC of patients who remained seizure-free (or had auras only) after surgery was significantly higher (p = 0.013) (2.53 pmol ME-1r mg-1 protein; n = 26; median) versus those patients who continued to have postsurgical seizures (or had no change) (0.64 pmol ME-1r mg-1 protein, n = 14; median).