Dextromethorphan and phencyclidine receptor ligands: differential effects on K(+)- and NMDA-evoked increases in cytosolic free Ca2+ concentration.

Abstract

The ability of dextromethorphan (DXM) and phencyclidine (PCP) receptor ligands to attenuate increases in cytosolic free Ca2+ concentration ([Ca2+]i) evoked by N-methyl-D-aspartate (NMDA) and high extracellular [K+] was examined using the fluorescent dye Fura 2 in cultured rat hippocampal pyramidal neurons. The DXM receptor ligand caramiphen (40 microM) reduced K(+)-evoked rises in [Ca2+]i to a greater extent than NMDA-evoked rises; the reverse was true for the PCP receptor ligands ketamine (10-40 microM) and dextrorphan (10 microM). DXM itself, which has affinity for both DXM and PCP receptors, reduced both K(+)- and NMDA-evoked increases in [Ca2+]i in a concentration-dependent manner. The results suggest that DXM receptor ligands may at least in part exert their known anticonvulsant and neuroprotective effects by reducing Ca2+ influx through voltage-activated Ca2+ channels.