Potentiation of NMDA Currents by Pituitary Adenylate Cyclase Activating Polypeptide in Neonatal Rat Sympathetic Preganglionic Neurons

Document Type

Article

Publication Date

1-1-1997

Description

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 μM). Further, superfusing the slices with the membrane-permeable cyclic AMP analogue N6,2'-0-dibutyryladenosine 3'-5'- cyclic monophosphate (100-300 μM) in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (700 μM) 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.

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