Effect of nociceptin/orphanin FQ and endomorphin-1 on glutamate and GABA release, intracellular [Ca2+] and cell excitability in primary cultures of rat cortical neurons.

The effects of nociceptin/orphanin FQ (N/OFQ) and endomorphin-1 (EM-1) on glutamate and GABA release, intracellular calcium, neuronal excitability and glutamate current were investigated in rat primary cortical neuronal cultures. Through their specific receptors N/OFQ and EM-1 (0.02-1 microM) inhibited the electrically evoked outflow of [3H]D-aspartate at most to -50% and that of [3H]GABA to -30%. In addition, at 1 microM, both peptides induced a decrease of the firing rate caused by electrical depolarization. N/OFQ 1-10 microM did not influence either the electrically evoked calcium influx or the glutamate-evoked currents, whereas EM-1 1 microM significantly inhibited them. Thus, in cortical neurons in culture, both N/OFQ and EM-1 inhibited the secretory process and neuronal excitability but EM-1 also affected calcium influx and cell body responsiveness to glutamate. Consequently, EM-1 appeared to dampen this excitatory signal more then N/OFQ did.