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J. Wang, A. Xie, J. Yan, R. F. Standaert, H. Qian, D. R. Pepperberg, L. J. Frishman; In vivo Effects of 2-AEMP Analog of GABA, a GABAc Receptor Antagonist, on Dark-Adapted Mouse ERG. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2179.
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To compare effects of 2-aminoethyl methylphosphonate (2-AEMP) analogue of GABA, recently reported to have GABAc antagonist properties in vitro in Xenopus oocytes (Chowdhury et al., 2007), with effects of a known GABAc receptor antagonist, 1, 2, 5, 6-tetrahydropyridine -4-yl-methylphosphinic acid (TPMPA), in vivo.
Dark-adapted ganzfeld ERGs were recorded from anesthetized C57BL/6 mice before and after intravitreal injection of TPMPA (50 µM vitreal conc. (vc), n=4) and 2-AEMP (1 mM vc, n=5), in response to brief flashes (-6.0 to 3.1 log sc td s). After oscillatory potentials (OPs > 50 Hz) were removed, ERG amplitudes were measured at the peak of the scotopic b-wave,110 ms after flash onset, and between a-wave trough and b-wave peak. For OP amplitude, the area under the OP power spectral density curve, i.e. total power, was calculated. Recordings (whole-cell voltage clamp) also were made from bipolar cells enzymatically isolated from rat retina.
Injection of TPMPA attenuated b-wave amplitudes, commencing at -2.6 log sc td s, and increasing up to b-wave saturation (-0.9 log sc td s), and then remaining at 49±8% reduction for measurements at 110 ms, and similarly by 45±6% for trough to peak amplitudes. Injection of 2-AEMP slightly attenuated b-wave amplitudes around -3.2 log sc td s, and the attenuation increased up to b-wave saturation (-0.9 log sc td s) with 31±9% reduction at 110 ms, and 25±9% for peak to trough. Neither agent affected a-waves. TPMPA and 2-AEMP increased OP amplitudes starting from -0.8 and -0.5 log sc td s, respectively. Above b-wave saturation, OP amplitudes exhibited a 72±35% increase with TPMPA, and a 150±57% increase with 2-AEMP. In isolated rat bipolar cells, 2-AEMP exhibited GABA antagonist activity that preferentially inhibited GABAc receptors.
Effects of a newly developed GABAc antagonist 2-AEMP and a known antagonist TPMPA are similar in vivo, causing b-wave attenuation and enhancement of OPs of the dark-adapted mouse ERG.
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