DUAL ACTIVATION OF GABA-A AND GLYCINE RECEPTORS BY BETA-ALANINE - INVERSE MODULATION BY PROGESTERONE AND 5-ALPHA-PREGNAN-3-ALPHA-OL-20-ONE

The differential sensitivity of the glycine and GABA(A) receptors to modulation by progesterone and 5alpha-pregnan-3alpha-ol-20-one (5alpha3alpha) was used to determine whether beta-alanine acts through its own receptor, or through the glycine and/or GABA(A) receptor(s). The response to beta-alanine resembles the glycine response as it is inhibited by strychnine (a competitive glycine antagonist) or progesterone (a negative modulator of the glycine response). Significantly, the response to beta-alanine also resembles the GABA response in that it is inhibited by 2-(carboxy-3'-propyl)-3-amino-6-paramethoxy-phenylpyridazinium bromide (SR-95531; a competitive GABA antagonist) and potentiated by 5alpha3alpha (a positive modulator of the GABA response). The efficacy of beta-alanine at the GABA(A) receptor is comparable to that of GABA. Similarly, the efficacy of beta-alanine at the glycine receptor is comparable to that of glycine. The greater potency of beta-alanine at the glycine receptor indicates that, if beta-alanine is a neurotransmitter, its effects are more likely to be mediated by glycine receptors than by GABA(A) receptors. However, activation of the GABA(A) receptor by beta-alanine may become important in the presence of steroid modulators such as progesterone or 5alpha3alpha.