A comparison of gamma-aminobutyric acid and the semi-rigid analogues 4-aminotetrolic acid, 4-aminocrotonic acid and imidazole-4-acetic acid on the isolated superior cervical ganglion of the rat.
1 The rat superior cervical ganglion possesses receptors for gamma-aminobutyric acid (GABA). This can be demonstrated in vitro by recording the changes in ganglionic surface potential which occur after the addition of GABA to the bathing solution. 2 The action of three conformationally-restricted analogues of GABA namely 4-aminotetrolic acid (4-ATA), trans 4-aminocrotonic acid (4-ACA) and imidazole-4-acetic acid (IAA) have been examined for activity at this peripheral receptor. 3 All three analogues depolarized the ganglion in a manner similar to GABA. Their actions were transient and were 'occluded' by GABA; also the dose-response curve in each case was parallel to that of GABA. Molar potencies relative to GABA (= 1) were 4-ACA = 1.48, IAA = 0.100, 4-ATA = 0.0028. 4 The action of each analogue could be blocked by the GABA antagonists bicuculline and tetramethylenedisulphotetramine at doses which had relatively little effect on responses to the cholinomimetic carbachol. 5 4-ACA and IAA (1 mM) significantly reduced the ganglionic accumulation of [3H]-GABA (0.2 muM) by 88% and 58% respectively whereas 4-ATA (1 mM), caused no significant reduction in [3H]-GABA accumulation.
D000613:Aminobutyrates / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects*; D066298:In Vitro Techniques; D008968:Molecular Conformation; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
D000613:Aminobutyrates; D009467:Neuromuscular Depolarizing Agents; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline