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

Neuropharmacology. 2004 Nov;47(6):873-83. doi: 10.1016/j.neuropharm.2004.06.017.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Calcium / metabolism*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism*
  • Electric Stimulation
  • Glutamic Acid / metabolism*
  • Ion Channel Gating / drug effects
  • Narcotic Antagonists / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oligopeptides / antagonists & inhibitors
  • Oligopeptides / pharmacology*
  • Opioid Peptides / antagonists & inhibitors
  • Opioid Peptides / pharmacology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid / drug effects
  • Tetrodotoxin / pharmacology
  • Vasodilator Agents / pharmacology*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Analgesics, Opioid
  • Narcotic Antagonists
  • Oligopeptides
  • Opioid Peptides
  • Receptors, Opioid
  • Vasodilator Agents
  • endomorphin 1
  • Glutamic Acid
  • Tetrodotoxin
  • gamma-Aminobutyric Acid
  • nociceptin
  • Calcium