A STUDY OF IMIDAZOLE-BASED NUCLEAR-MAGNETIC-RESONANCE PROBES OF CELLULAR PH

A number of imidazole-based compounds were tested for their utility as H-1 NMR molecular probes of intracellular pH. Imidazole, previously f ound useful as a probe of erythrocyte pH, reported a pH in perfused ca nine glioma cells that was more than 1 pH unit lower than that reporte d by inorganic phosphate, consistent with the known lysosomal compartm entation of the molecule. Imidazole acetate, also proposed as an NMR p robe of cellular pH, was found not to enter the cells of this study. H istidine was found to be readily taken up by cells and reported a pH c onsistent with that reported by inorganic phosphate. Using the chemica l shift of the histidine H2 proton in cells incubated with 10 mM histi dine, cellular pH measurements could be obtained in less than 1 s. Thi s compares quite favorably with the measurement time, typically severa l minutes, needed to assess in vivo pH by P-31 NMR. The use of histidi ne as a probe of pH is demonstrated in perfused canine and rat glioma cells subjected to ischemia or to low extracellular pH. (C) 1998 Acade mic Press.