Homotaurine: a GABAB antagonist in guinea‐pig ileum

Abstract

1 Homotaurine (3-aminopropane sulphonic acid) did not inhibit the twitch response in guinea-pig ileum longitudinal muscle whilst γ-aminobutyric acid (GABA) and (−)-baclofen evoked dose-dependent inhibitions. 2 The inhibitory effects of GABA and (−)-baclofen were prevented in the presence of homotaurine 2 × 10⁻⁴ and 10⁻³ M. 3 The log dose-effect curves of GABA and (−)-baclofen were shifted in a parallel manner compatible with competitive antagonism. The pA₂ of homotaurine with GABA (4.22 ± 0.05) and (−)-baclofen (4.26 ± 0.1) were the same. 4 Homotaurine did not antagonize the inhibitory effects of morphine (ED₅₀ 4 × 10⁻⁷ M), noradrenaline (ED₅₀ 10⁻⁶ M) or ATP (ED₅₀ 1.5 × 10⁻⁵ M). 5 The inferior homologue of homotaurine, taurine 10⁻³ M, did not modify the inhibitory effects of GABA and (−)-baclofen. 6 Picrotoxin 5 × 10⁻⁵ M antagonized GABA_A receptor-mediated contraction but did not affect GABA_B receptor-mediated inhibition. At the same concentration the drug did not influence the antagonistic action of homotaurine, thus showing no GABA_A receptor-mediated interference. 7 It may be concluded that homotaurine is a competitive antagonist of GABA_B mediated effects in the guinea-pig ileum.