Extracts of retina and brain that excite afferent fibers innervating hair cells contain a compound related to hydroxyphenylglycine-N-carbamoyl.

To identify new neurotransmitter and modulator candidates that might be important in transmission from sensory hair cells to afferent nerves, we examined extracts of neural tissue for compounds that excite afferent fibers innervating hair cells. Here, we describe the extraction and purification from retina and brain of a potent, unstable, excitatory compound with pharmacological activity similar to glutamate on afferent fibers innervating hair cells. This compound, however, was clearly distinguished from glutamate, other common amino acids, and known endogenous glutamate-receptor agonists. After derivatization and analysis by gas chromatography-mass spectrometry, the major compound found in highly purified neuroactive chromatographic fractions had the same gas chromatographic elution time and mass spectrum as the compound formed by derivatization of L-p-hydroxyphenylglycine-N-carbamoyl. Hydroxyphenylglycine-N-carbamoyl, however, did not copurify with the neuroactive compound and was not neuroactive. We thus hypothesize that the detected compound was produced from a precursor, structurally related to L-p-hydroxyphenylglycine-N-carbamoyl, that was a major component of the neuroactive chromatographic fractions. Because several compounds related to hydroxyphenylglycine are known to act on glutamate receptors, such a compound is an interesting candidate to be an endogenous glutamate-receptor ligand in the mammalian nervous system. (c) 2005 Wiley-Liss, Inc.