Potentiation of NMDA currents by pituitary adenylate cyclase activating polypeptide in neonatal rat sympathetic preganglionic neurons

J Neurophysiol. 1997 Aug;78(2):1175-9. doi: 10.1152/jn.1997.78.2.1175.


Whole cell patch-clamp recordings were made from sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column of thoracolumbar spinal cord slices of 12- to 16-day-old rats, and the effects of pituitary adenylate cyclase activating polypeptide (PACAP)-38 on N-methyl-D-aspartate (NMDA)- and kainate (KA)-induced inward currents were examined. PACAP, in concentrations (10-30 nM) that caused no significant change of holding currents, reversibly increased NMDA-induced currents but not KA-induced currents. At higher concentrations (>30 nM), the peptide produced a sustained inward current. The potentiating effect of PACAP was nullified by prior incubation of the slices with the adenylate cyclase inhibitor MDL-12,330A (25 microM). Further, superfusing the slices with the membrane-permeable cyclic AMP analogue N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (100-300 microM) in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (700 microM) increased the NMDA currents. This result suggests that PACAP selectively increases NMDA-receptor-mediated responses in the rat SPNs, probably via a cyclic-AMP-dependent mechanism, providing evidence that the peptide may be involved in synaptic plasticity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / physiology*
  • Animals
  • Animals, Newborn
  • Autonomic Fibers, Preganglionic / physiology*
  • Glutamic Acid / physiology
  • Immunohistochemistry
  • In Vitro Techniques
  • Neurons / physiology*
  • Neuropeptides / physiology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Spinal Cord / cytology
  • Spinal Cord / physiology
  • Sympathetic Nervous System / physiology*


  • Adcyap1 protein, rat
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Adenylyl Cyclases