Extracellular loops 2 and 4 of GLYT2 are required for N-arachidonylglycine inhibition of glycine transport.

ABSTRACT: Concentrations of extracellular glycine in the central nervous system are regulated by Na(+)/Cl(-)-dependent glycine transporters, GLYT1 and GLYT2. N-Arachidonylglycine (NAGly) is an endogenous inhibitor of GLYT2 with little or no effect on GLYT1 and is analgesic in rat models of neuropathic and inflammatory pain. Understanding the molecular basis of NAGly interactions with GLYT2 may allow for the development of novel therapeutics. In this study, chimeric transporters were used to determine the structural basis for differences in NAGly sensitivity between GLYT1 and GLYT2 and also the actions of a series of related N-arachidonyl amino acids. Extracellular loops 2 and 4 of GLYT2 are important in the selective inhibition of GLYT2 by NAGly and by the related compounds N-arachidonyl-gamma-amino

SUBMITTER: Edington AR 

PROVIDER: S-EPMC2794758 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature