PACAP38 modulates activity of NMDA receptors in cultured chick cortical neurons

J Neurophysiol. 1997 Oct;78(4):2231-4. doi: 10.1152/jn.1997.78.4.2231.


The outside-out recording mode of the patch-clamp technique was used to study modulatory effects of pituitary adenylate cyclase-activating polypeptide (PACAP38) on N-methyl--aspartate (NMDA) receptor activity in cultured chick cortical neurons. Biphasic concentration-dependent effects of PACAP38 on channel opening frequency induced by NMDA (20 microM) and glycine (1 microM) were found, with low concentrations (0.5-2 nM) of PACAP38 increasing activity and higher concentrations (10-1,000 nM) causing inhibition. These effects were reversible, reduced with higher concentrations of glycine (2-10 microM) but not by 200 microM NMDA, and inhibited by 10 microM 7-chlorokynurenic acid. In addition, 1 microM PACAP6-38 (a PACAP antagonist) inhibited channel activity due to 20 microM NMDA and 1 microM glycine by 66%, and this inhibition was reduced to 13% in the additional presence of 2 nM PACAP38. These observations suggest that PACAP38 has a direct modulatory effect on the NMDA receptor that is independent of intracellular second messengers and probably mediated through the glycine coagonist site(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cerebral Cortex / drug effects*
  • Chick Embryo
  • Glycine / pharmacology
  • Neurons / drug effects
  • Neuropeptides / pharmacology*
  • Neurotransmitter Agents / pharmacology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, N-Methyl-D-Aspartate / drug effects*


  • Neuropeptides
  • Neurotransmitter Agents
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, N-Methyl-D-Aspartate
  • Glycine