Uraemic guanidino compounds inhibit gamma-aminobutyric acid-evoked whole cell currents in mouse spinal cord neurones.
Guanidine, creatinine (CTN), methylguanidine (MG) and guanidinosuccinic acid (GSA) are four endogenous guanidino compounds with proven neuroexcitatory actions, and putative pathophysiological significance as uraemic toxins. The effects of these uraemic guanidino compounds, were studied on whole-cell current evoked by gamma-amino butyric acid (GABA) on mouse spinal cord neurones in vitro. CTN, MG and GSA concentration dependently blocked GABA-evoked 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 inward and outward currents to the same extent, demonstrating voltage independent block of GABA-evoked current by these compounds. Guanidine, however, evoked inward whole-cell currents, which were almost completely blocked by strychnine, indicating that the guanidine-evoked current might have been due to glycine receptor activation.
D000818:Animals; D002478:Cells, Cultured; D003404:Creatinine / Q000494:pharmacology*; D004553:Electric Conductivity; D004594:Electrophysiology; D006146:Guanidines / Q000378:metabolism / Q000494:pharmacology*; D008760:Methylguanidine / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009994:Osmolar Concentration; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013386:Succinates / Q000494:pharmacology; D014511:Uremia / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*