The taurine uptake inhibitor guanidinoethyl sulphonate is an agonist at gamma-aminobutyric acid(A) receptors in cultured murine cerebellar granule cells.
In patch clamp experiments the beta-amino acid uptake inhibitor guanidinoethyl sulphonate (GES) activated currents in intact cultured murine cerebellar granule neurones. These responses could be attenuated by the gamma-aminobutyric acid(A) (GABA(A)) receptor antagonists bicuculline and picrotoxin. With intracellular chloride concentrations of either 20 or 130 mM, GES-induced current responses reversed polarity near the chloride equilibrium potential. When fast applications of agonist were made to excised granule cell macropatches GES responses were dose-dependent and exhibited significant outward rectification. Like taurine (but unlike GABA and beta-alanine) responses, macroscopic desensitisation of GES-induced currents was slow. Our data indicate that care should be exercised when using GES as a taurine uptake inhibitor in systems that also contain GABA(A) receptors.
Mellor
J R
JR
Neuroscience Research, SmithKline Beecham Pharmaceuticals, Third Avenue, Essex, CM19 5AW, Harlow, UK.
Gunthorpe
M J
MJ
Randall
A D
AD
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013654:Taurine / Q000031:analogs & derivatives* / Q000187:drug effects* / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors
D001640:Bicuculline; D002712:Chlorides; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D010852:Picrotoxin; D011963:Receptors, GABA-A; D013654:Taurine; C009558:taurocyamine