Taurine receptor: kinetic analysis and pharmacological studies.
A new procedure for the preparation of the taurine receptor from mammalian brain is described. The taurine receptor thus prepared shows a Kd of 92 nM, Bmax of 6.0 pmol/mg protein and Hill coefficient of 0.90 suggesting a single site model for the binding of 3H-taurine to the receptor. The binding of 3H-taurine to the receptor is highly specific and is not affected by agonists and antagonists of other receptors such as glutamate, quisqualic acid, kainate and NMDA for the glutamate receptor; glycine and strychnine for the glycine receptor; FNZP for the benzodiazepine receptor; picrotoxin and bicuculline for the GABAB receptor. However, analogues of taurine (e.g., homotaurine and hypotaurine) are potent inhibitors inhibiting more than 50% of 3H-taurine binding at 0.1 microM. Taurine receptor binding is not significantly affected by monovalent cations (e.g., Na+, K+, Li+ and NH4+) at 1 mM or divalent cations (e.g., Mg2+, Ca2+, Ba2+ and Mn2+) at 0.1 mM. However, the binding was completely abolished by Co2+, Zn2+ and Hg2+ at 0.1 mM, suggesting the presence of free sulfhydryl groups near or at the ligand binding site. Among the amino acids tested, cysteic acid was the most potent inhibitor, followed by beta-alanine, valine, tyrosine and cysteine inhibiting 3H-taurine to an extent of 84, 66, 63, 62, and 58% of 1 mM, respectively. Nucleotides and second messengers (e.g., ATP, ADP, cAMP, GTP, cGMP and diacyl glycerol) do not inhibit 3H-taurine binding significantly at 0.1 mM. From above studies, it seems that the taurine receptor is not up- or down-regulated by ions or second messengers at the taurine binding site. Whether the taurine receptor is coupled to a G-protein mediated second messenger system is currently under investigation.
Wu
J Y
JY
Department of Physiology and Cell Biology, University of Kansas, Lawrence 66045.
Tang
X W
XW
Tsai
W H
WH
D000596:Amino Acids / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002412:Cations / Q000494:pharmacology; D007700:Kinetics; D009711:Nucleotides / Q000494:pharmacology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D015290:Second Messenger Systems / Q000502:physiology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000596:Amino Acids; D002412:Cations; D009711:Nucleotides; D017981:Receptors, Neurotransmitter; C030803:taurine receptor; D013654:Taurine