Modulation of neuronal mitochondrial membrane potential by the NMDA receptor: role of arachidonic acid.
Activation of NMDA receptors in dissociated cerebellar granule cells reduced mitochondrial membrane potential (MMP), as measured by rhodamine 123 fluorescence in a flow cytometer. This effect was inhibited by several NMDA-receptor antagonists with the following rank order of potency: MK-801 > PCP > TCP > dextrorphan > dichlorokynurenic acid > D-AP5 > dextromethorphan. Neither spermine nor arcaine modified the NMDA-induced reduction in MMP, whereas ifenprodil and eliprodil inhibited this response in the micromolar range. The mechanism responsible for the alteration of MMP mediated by NMDA was studied. Mepacrine and dibucaine prevented the MMP reduction induced by NMDA, as did W13 (calmodulin antagonist). In contrast, this effect was not blocked by cyclooxygenase or lipooxygenase inhibitors, H7 (a protein kinase C inhibitor) or nitroarginine (nitric oxide synthase inhibitor). These data suggest a direct interaction between NMDA-receptor activation and arachidonic acid formation, and indicate that NMDA receptor-mediated effect on MMP could involve arachidonic acid.
Camins
A
A
Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Spain.
Sureda
F X
FX
Gabriel
C
C
Pallàs
M
M
Escubedo
E
E
Camarasa
J
J
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D015415:Biomarkers; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003992:Dibucaine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005998:Glycine / Q000494:pharmacology; D007425:Intracellular Membranes / Q000737:chemistry / Q000502:physiology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000737:chemistry* / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D020112:Rhodamine 123; D012235:Rhodamines; D013449:Sulfonamides / Q000494:pharmacology
D000779:Anesthetics, Local; D015415:Biomarkers; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D012235:Rhodamines; D013449:Sulfonamides; D020112:Rhodamine 123; D016718:Arachidonic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D007736:Kynurenic Acid; D011796:Quinacrine; D003992:Dibucaine; C010739:ifenprodil; C066192:5,7-dichlorokynurenic acid; D005998:Glycine; C058083:eliprodil