Dextromethorphan and phencyclidine receptor ligands: differential effects on K(+)- and NMDA-evoked increases in cytosolic free Ca2+ concentration.
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.
Church
J
J
Department of Physiology, University of British Columbia, Vancouver, Canada.
Shacklock
J A
JA
Baimbridge
K G
KG
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003517:Cyclopentanes / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D003915:Dextromethorphan / Q000494:pharmacology*; D005260:Female; D016257:Fura-2; D006624:Hippocampus / Q000166:cytology; D007649:Ketamine / Q000494:pharmacology; D008024:Ligands; D016202:N-Methylaspartate / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011247:Pregnancy; D011712:Pyramidal Tracts / Q000166:cytology; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D017478:Receptors, Phencyclidine
D003517:Cyclopentanes; D008024:Ligands; D010276:Parasympatholytics; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D016202:N-Methylaspartate; D007649:Ketamine; D003915:Dextromethorphan; C004519:caramiphen; D011188:Potassium; D002118:Calcium; D016257:Fura-2