Recent evidence suggests that the N-methyl-D-aspartate (N-Me-D-Asp) channel is functionally and structurally associated with the phencyclidine (PCP) receptor, which mediates the psychotomimetic effects of PCP, a opioids, and dioxalanes. To investigate the relationship between N-Me-D-Asp and PCP receptors on a molecular level, we injected mRNA isolated from adult rat brain into Xenopus oocytes. In injected oocytes N-Me-D-Asp application (with glycine) evoked a partially desensitizing inward current that was potentiated by glycine and blocked by D-(-)-amino-5-phosphonovaleric acid (D-APV), by Zn2' and, in a voltage-dependent manner, by Mg2 . These results show that the distinguishing features ofrat brain N-Me-D-Asp channels are reproduced in this translation system. In addition, kainic acid elicited a nondesensitizing inward current at short latency, and quisqualate elicited a delayed oscillatory inward current, presumably mediated by a second-messenger system. Responses to glutamate had both short-latency and delayed components. (21) Autoradiographic studies demonstrate that the two receptors are colocalized in rat forebrain and midbrain (24,25). However, N-Me-D-Asp receptors occur independently of PCP receptors in the cerebellum (25).The Xenopus oocyte is a self-contained expression system that is particularly suitable for the study of the relationship between receptor structure and function and for identifying the mRNA that directs receptor synthesis. This system has been shown to faithfully translate neuroreceptor (23,(26)(27)(28) and channel (29,30)