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N [3‐(4′‐fluorophenyl)‐3‐(4′‐phenylphenoxy)propyl]sarcosine (NFPS) is a selective persistent inhibitor of glycine transport
Author(s) -
Aubrey Karin R,
Vandenberg Robert J
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704381
Subject(s) - sarcosine , glycine , glycine receptor , chemistry , transporter , biophysics , xenopus , biochemistry , amino acid , serine , stereochemistry , biology , enzyme , gene
The regulation of glycine concentrations within excitatory synapses is poorly understood and it has been proposed that the GLYT1 subtypes of glycine transporters play a critical role in determining resting concentrations of glycine. Selective GLYT1 inhibitors may provide pharmacological tools to probe the dynamics of synaptic glycine concentrations, which may influence the activation properties of NMDA receptor activity. We have characterized the selectivity and mechanism of action of the glycine transport inhibitor N [3‐(4′‐fluorophenyl)‐3‐(4′‐phenylphenoxy)propyl]sarcosine (NFPS). The glycine transporters, GLYT1a, b and c and GLYT2a were expressed in Xenopus laevis oocytes and two electrode voltage clamp techniques and radiolabelled 3 H‐glycine flux measurements were used to characterize the effects of NFPS on glycine transport. NFPS inhibits glycine transport by the GLYT1a, b and c subtypes of glycine transporters, but has no effect on the GLYT2a subtype of transporter. We show that NFPS does not attain its specificity via an interaction with the Na + , Cl − or glycine site, nor does it act at an intracellular site. NFPS inhibition of glycine transport is time and concentration dependent and inhibition of transport by NFPS persists after washout of NFPS from the bath solution, which suggests that inhibition by NFPS is long lasting.British Journal of Pharmacology (2001) 134 , 1429–1436; doi: 10.1038/sj.bjp.0704381