Wu, S. Y. and N. J. Dun. Potentiation of NMDA currents by pituitary adenylate cyclase activating polypeptide in neonatal rat sympathetic preganglionic neurons. J. Neurophysiol. 78: 1175–1179, 1997. 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.
Correction: Lot1 is a key element of the pituitary adenylate cyclase-activating polypeptide (PACAP)/cyclic AMP pathway that negatively regulates neuronal precursor proliferation.
