Efflux of rubidium in rat cortical synaptosomes is blocked by sigma and dextromethorphan binding site ligands.
Large concentrations of potassium were used to stimulate the release of rubidium-86 from preloaded cortical synaptosomes, so that the pharmacological sensitivity of this efflux could be examined. Potassium channel blockers, 4-aminopyridine and tetraethylammonium, inhibited the evoked release of rubidium. Sigma ligands, e.g. pentazocine, cyclazocine, rimcazole, 1,3-di(2-tolyl)guanidine (DTG) and haloperidol, as well as the antitussives, carbetapentane, caramiphen and dextromethorphan, significantly reduced potassium-stimulated efflux of rubidium. By contrast, 3-hydroxyphenyl-propylpiperidine (3-PPP), 5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine (MK-801), phencyclidine (PCP), ketamine and D-2-amino-5-phosphonovalerate (D-AP5) were all inactive. This suggests that inhibition of potassium-stimulated efflux of rubidium is correlated with activity at the sigma and/or dextromethorphan binding sites rather than at the N-methyl-D-aspartate (NMDA)/PCP receptor-channel complex.
Fletcher
E J
EJ
Department of Basic Veterinary Sciences, Royal Veterinary College, London, U.K.
Drew
C
C
Lodge
D
D
O'Shaughnessy
C T
CT
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003915:Dextromethorphan / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007981:Levorphanol / Q000031:analogs & derivatives*; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017480:Receptors, sigma; D012413:Rubidium / Q000378:metabolism*; D012414:Rubidium Radioisotopes; D013574:Synaptosomes / Q000378:metabolism*
D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017480:Receptors, sigma; D012414:Rubidium Radioisotopes; D007981:Levorphanol; D011189:Potassium Chloride; D003915:Dextromethorphan; D012413:Rubidium