Uraemic guanidino compounds inhibit gamma-aminobutyric acid-evoked whole cell currents in mouse spinal cord neurones

Guanidine, creatinine (CTN), methylguanidine (MG) and guanidinosuccinic aci d (GSA) are four endogenous guanidino compounds with proven neuroexcitatory actions, and putative pathophysiological significance as uraemic toxins, T he effects of these uraemic guanidino compounds, were studied on whole-cell current evoked by gamma-amino butyric acid (GABA) on mouse spinal cord neu rones in vitro. CTN, MG and GSA concentration dependently blocked GABA-evok ed current with calculated IC50 values (+/-SE) of 9.6 +/- 0.9, 9.7 +/- 1.5 and 5.1 +/- 0.4 mM, respectively. CTN, MG and GSA were shown to block inwar d and outward currents to the same extent, demonstrating voltage independen t block of GABA-evoked current by these compounds. Guanidine, however, evok ed inward whole-cell currents, which were almost completely blocked by stry chnine, indicating that the guanidine-evoked current might have been due to glycine receptor activation. (C) 1999 Elsevier Science Ireland Ltd. All ri ghts reserved.