Dual activation of GABA A and glycine receptors by β-alanine: inverse modulation by progesterone and 5α-pregnan-3α-ol-20-one

Abstract

The differential sensitivity of the glycine and GABA A receptors to modulation by progesterone and 5α-pregnan-3α-ol-20-one (5α3α) was used to determine whether β-alanine acts through its own receptor, or through the glycine and/or GABA A receptor(s). The response to β-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 β-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 5α3α (a positive modulator of the GABA response). The efficacy of β-alanine at the GABA A receptor is comparable to that of GABA. Similarly, the efficacy of β-alanine at the glycine receptor is comparable to that of glycine. The greater potency of β-alanine at the glycine receptor indicates that, if β-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 β-alanine may become important in the presence of steroid modulators such as progesterone or 5α3α.