Characterization of bicuculline/baclofen-insensitive (rho-like) gamma-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of gamma-aminobutyric acidA and gamma-aminobutyric acidB receptor agonists and antagonists

Mol Pharmacol. 1993 Apr;43(4):609-25.


Poly(A)+ RNA from mammalian retina expresses bicuculline/baclofen-insensitive gamma-aminobutyric acid (GABA) receptors in Xenopus oocytes with properties similar to those of homooligomeric GABA rho 1 receptors. The pharmacological profile of these rho-like receptors was extended by measuring sensitivities to various GABAA and GABAB receptor ligands. For direct comparison the same compounds were also assayed with GABAA receptors expressed by rat brain RNA. The potency sequence for heterocyclic GABA analogues at the GABA rho-like receptors was GABA (1.3) > muscimol (2.3) > isoguvacine (100) (approximate EC50 in parentheses; all EC50 and Kb values given in microM). Both muscimol and isoguvacine were partial agonists at the rho-like receptors. 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol (Kb congruent to 32), piperidine-4-sulfonic acid (Kb congruent to 85), and isonipecotic acid (Kb congruent to 1000) acted primarily as competitive antagonists, showing little or no activity as agonists. The sulfonic acid GABA analogue 3-aminopropanesulfonic acid was also a competitive antagonist (Kb congruent to 20). Conformationally restricted GABA analogues trans- and cis-4-aminocrotonic acid (TACA and CACA) were agonists at the rho-like receptors. TACA (EC50 congruent to 0.6) had twice the potency of GABA and was 125 times more potent than CACA (EC50 congruent to 75). Z-3-(Amidinothio)propenoic acid, an isothiouronium analogue of GABA, had little activity as an agonist but instead acted as a competitive antagonist (Kb congruent to 20). At concentrations of > 100 microM, bicuculline did have some weak competitive inhibitory effects on the GABA rho-like receptors (Kb congruent to 6000), but it was at least 5000 times more potent at GABAA receptors. Strychnine (Kb congruent to 70) and SR-95531 (Kb congruent to 35) also were competitive inhibitors of the rho-like receptors but were, respectively, 20 and 240 times more potent at GABAA receptors. The GABAB receptor ligands baclofen, phaclofen, and saclofen (1-100 microM) had no appreciable effects on the rho-like receptors. In contrast, 3-aminopropylphosphonic acid, the phosphonic acid analogue of GABA, acted as a competitive antagonist (Kb congruent to 10), and 3-aminopropylphosphinic acid and 3-aminopropyl(methyl)-phosphinic acid were moderately potent antagonists (Kb congruent to 1.7 and 0.8, respectively). delta-Aminovaleric acid was also an antagonist (Kb congruent to 20), whereas 4-aminobutylphosphonic acid, the phosphonic acid analogue of delta-aminovaleric acid, was only a weak inhibitor (Kb congruent to 600).(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Bicuculline / pharmacology
  • Brain / drug effects
  • Cattle
  • Chloride Channels
  • Chlorides / physiology
  • Female
  • GABA-A Receptor Antagonists
  • In Vitro Techniques
  • Ligands
  • Membrane Proteins / drug effects
  • Oocytes / metabolism
  • Rats
  • Receptors, GABA-A / biosynthesis
  • Receptors, GABA-A / classification
  • Receptors, GABA-A / drug effects*
  • Recombinant Proteins / biosynthesis
  • Xenopus


  • Chloride Channels
  • Chlorides
  • GABA-A Receptor Antagonists
  • Ligands
  • Membrane Proteins
  • Receptors, GABA-A
  • Recombinant Proteins
  • Baclofen
  • Bicuculline