Homotaurine: a GABAB antagonist in guinea-pig ileum.
Homotaurine (3-aminopropane sulphonic acid) did not inhibit the twitch response in guinea-pig ileum longitudinal muscle whilst gamma-aminobutyric acid (GABA) and (-)-baclofen evoked dose-dependent inhibitions. The inhibitory effects of GABA and (-)-baclofen were prevented in the presence of homotaurine 2 X 10(-4) and 10(-3) M. 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. Homotaurine did not antagonize the inhibitory effects of morphine (ED50 4 X 10(-7) M), noradrenaline (ED50 10(-6) M) or ATP (ED50 1.5 X 10(-5) M). The inferior homologue of homotaurine, taurine 10(-3) M, did not modify the inhibitory effects of GABA and (-)-baclofen. Picrotoxin 5 X 10(-5) M antagonized GABAA receptor-mediated contraction but did not affect GABAB receptor-mediated inhibition. At the same concentration the drug did not influence the antagonistic action of homotaurine, thus showing no GABAA receptor-mediated interference. It may be concluded that homotaurine is a competitive antagonist of GABAB mediated effects in the guinea-pig ileum.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004558:Electric Stimulation; D018756:GABA Antagonists; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D001418:Baclofen; D018756:GABA Antagonists; D010852:Picrotoxin; D013654:Taurine; C001355:tramiprosate