FIGURE SUMMARY
Title

Identification of the hypertension drug niflumic acid as a glycine receptor inhibitor

Authors
Ito, D., Kawazoe, Y., Sato, A., Uesugi, M., Hirata, H.
Source
Full text @ Sci. Rep.
Figure 1

Bath application of strychnine, picrotoxin, nifedipine or niflumic acid to zebrafish embryos at 48 hpf caused abnormal touch response touch. (a) A superimposed image of 100 Hz movie frames. A control wild-type embryo (1% DMSO) responded to tactile stimulation and showed swimming by side-to-side trunk contractions. (b) Strychnine-treated embryos responded to touch by bilateral muscle contractions that resulted in shortening of the body along anterior–posterior axis. (c) Picrotoxin-treated embryos exhibited similar shrinkage of the body. (d) Nifedipine-treated embryos showed similar abnormal touch response. (e) Niflumic acid-treated embryos also responded to touch by bilateral muscle contractions.
Figure 2

Heteromeric GlyR decreased glycine sensitivity compared with homomeric GlyR. (a) A trace of two-electrode voltage-clamp recording from oocyte injected with five femtomoles of zGlyRα1 cRNAs exposed to serial application of glycine of increasing amounts. (b) Cumulative concentration–response relationship of glycine-evoked currents. The amplitude of glycine-evoked currents was normalized to the maximally-evoked current as 100% for each oocyte (n = 10). Values here and elsewhere represent mean ± SEM.
Figure 3

Drug-mediated inhibition of homomeric and heteromeric zebrafish GlyRs. (a) A recording from a zGlyRα1-injected oocyte exposed to 200 µM glycine with increasing amounts of niflumic acid. (b) Cumulative concentration-dependent inhibition of GlyRα1 current by strychnine, picrotoxin, nifedipine and niflumic acid (n = 10 each). (c) A recording from an oocyte, which were injected with zGlyRα1 and zGlyRβb and exposed to 200 µM glycine with increasing amounts of niflumic acid. (d) Cumulative concentration-curves of strychnine, picrotoxin, nifedipine and niflumic acid-mediated inhibition of α1/βb heteromeric zebrafish GlyRs (n = 10 each).
Figure 4

Drug-mediated inhibition of homomeric and heteromeric human GlyRs. (a) A recording from a hGlyRα1-injected oocyte exposed to 200 µM glycine with increasing amounts of niflumic acid. (b) Cumulative concentration-dependent inhibition of GlyRα1 current by strychnine, picrotoxin, nifedipine and niflumic acid (n = 10 each). (c) A recording from an oocyte, which were injected with hGlyRα1 and hGlyRβ and exposed to 200 µM glycine and increasing amounts of niflumic acid. (d) Cumulative concentration-curves of strychnine, picrotoxin, nifedipine and niflumic acid-mediated inhibition of α1/β heteromeric human GlyRs (n = 10 each).
Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Sci. Rep.
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