A COMPARISON OF γ‐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

Abstract

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.