Potentiation of NMDA currents by pituitary adenylate cyclase activating polypeptide in neonatal rat sympathetic preganglionic neurons.
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.
Wu
S Y
SY
Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo 43614, USA.
Dun
N J
NJ
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001339:Autonomic Fibers, Preganglionic / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000262:Adenylyl Cyclases