What confers specificity on glycine for its receptor site?

Abstract

1. The structural requirements for activation of the glycine receptor were studied in isolated ventromedial hypothalamic neurones of rats by use of a 'concentration-clamp' technique under single-electrode voltage-clamp conditions. 2. α-Amino acids (L-α-alanine, and D-α-alanine, and L-serine), and glycine-methylester, glycine-ethylester and β-amino acids (β-alanine and taurine) produced a transient inward Cl- current, which was similar to that induced by glycine. 3. The responses to individual α- and β-amino acids were selectively antagonized by strychnine, but were not affected by bicuculline, picrotoxin or the taurine antagonist, TAG (6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1,1-dioxide hydrochloride), suggesting that α- and β-amino acids activate the same glycine receptor. 4. β-Amino acids were slightly more potent than the α-amino acids in causing cross-desensitization of the glycine response. 5. From the results of the structure-activity analysis of the optical isomers of α-alanine, serine and cysteine, a tentative structure of the glycine receptor is proposed.