The Journal of Neurophysiology Vol. 78 No. 4 October 1997, pp. 2231-2234
Copyright ©1997 The American Physiological Society

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PACAP₃₈ Modulates Activity of NMDA Receptors in Cultured Chick Cortical Neurons

Guo Jun Liu and Barry W. Madsen

Department of Pharmacology, University of Western Australia, Nedlands WA 6907, Australia

Liu, Guo Jun and Barry W. Madsen. PACAP₃₈ modulates activity of NMDA receptors in cultured chick cortical neurons. J. Neurophysiol. 78: 2231-2234, 1997. 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-D-aspartate (NMDA) receptor activity in cultured chick cortical neurons. Biphasic concentration-dependent effects of PACAP₃₈ on channel opening frequency induced by NMDA (20 µM) and glycine (1 µM) 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 µM) but not by 200 µM NMDA, and inhibited by 10 µM 7-chlorokynurenic acid. In addition, 1 µM PACAP_6-38 (a PACAP antagonist) inhibited channel activity due to 20 µM NMDA and 1 µM glycine by 66%, and this inhibition was reduced to 13% in the additional presence of 2 nM PACAP₃₈. These observations suggest thatPACAP₃₈ 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).

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