5-Aminovaleric acid interactions with GABAA and GABAB receptors in guinea-pig ileum

The potential interaction of 5-aminovaleric acid (5-AVA) on GABAA and GABAB receptors was investigated on the guinea-pig isolated ileum myenteric plexus preparation. In the unstimulated preparation 5-AVA (0.1-3 mM) produced a transient contraction which was abolished by previous exposure to picrotoxin (0.1 mM), atropine (3 microM) or tetrodotoxin (0.3 microM). Cross desensitization was observed between the contractile effects of 5-AVA and GABA, while a previous exposure to (+/-)-baclofen did not affect 5-AVA induced contractions. 5-AVA antagonized the relaxant effect of (+/-)-baclofen in unstimulated preparations. 5-AVA (1 mM) had no effect on amplitude of twitches in supramaximally stimulated preparations while GABA produced a concentration related inhibition. In the presence of 5-AVA (1 mM) the concentration response curve to GABA was shifted to the right without a reduction of the maximal effect attainable. These observations indicate that 5-AVA interacts with both GABAA and GABAB receptors in guinea-pig ileum. The concentrations required to observe a GABAA effect are of the same order as those which are effective in producing a blockade of GABAB mediated responses.