ISSN:
1440-1681
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
1. A microfluorometry was carried out to investigate the effect of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (ibudilast) on changes in levels of intracellular calcium concentration ([Ca2+]i) induced by in vitro ischaemia in the CA1 field of gerbil hippocampal slices.2. When slices, loaded with a calcium ion sensitive dye (rhod-2) were exposed to a glucose-free physiological medium equilibrated with a 95% N2/5% CO2 gas mixture (standard in vitro ischaemia), a large [Ca2+]i elevation was detected approximately 5 min after the beginning of in vitro ischaemia.3. When slices were perfused with the in vitro ischaemic medium containing 43 μmol/L ibudilast, a [Ca2+]i elevation was still observed; however, the extent of the increase in [Ca2+]i was significantly depressed in all subregions of the hippocampal slices.4. The extent of this inhibitory effect of ibudilast on the in vitro ischaemia-induced [Ca2+]i elevation was in a similar range as those of Ca2+ blockers, including (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine maleate (MK-801), flunarizine and dantrolene.5. Similar [Ca2+]i increases in the CA1 field were induced by a Ca2+-free in vitro ischaemia, a high concentration of KCl or by specific agonists for glutamate receptor subtypes (N-methyl-d-aspartate (NMDA), (s)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate); these increases were also depressed with 43 μmol/L ibudilast present in the perfusion medium.6. These results indicate that ibudilast may act by depressing the Ca2+ accumulation during and shortly after ischaemia, a possible pharmacological action of ibudilast that leads to the amelioration of ischaemic injury in the central nervous system.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1440-1681.1996.tb02830.x
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