The modulatory effect of PACAP27 on NMDA receptor channel activity in cultured chick cortical neurons was investigated using the outside-out recording mode of the patch clamp technique. Channel opening frequency elicited by 20 microM NMDA, or 20 microM NMDA plus 1 microM glycine, was potentiated in the presence of 100 nM PACAP27 and inhibited with 1000 nM PACAP27. These effects were reversible on washout and reduced when glycine concentration was increased to 10 microM, but were not affected by the PACAP antagonist PACAP6-27 (1 microM) or the GTP inhibitor GDP-beta-S (100 microM). It is suggested that PACAP27 may exert its modulatory action on NMDA receptor channel activity through the glycine site(s).
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