2 TYPES OF FUNCTIONALLY DIFFERENT GABA(A) RECEPTORS MEDIATE GABA MODULATION OF CHOLINERGIC TRANSMISSION IN CAT TERMINAL ILEUM

1 The effects of GABA (1 mu M-2 mM) on longitudinally or circularly or iented organ bath preparations of cat terminal ileum consisted of a re laxation phase with an inhibition of the rhythmic spontaneous phasic c ontractions, followed by a phase of contractions characterized by an e levation in basal tone and an increase in amplitude of the spontaneous phasic contractions. 2 Muscimol (100 mu M), but not baclofen (100 mu M), mimicked the relaxation phase of the response to applied GABA (100 mu M) in all tissue preparations. In addition, muscimol induced a pha se of contractile activity in the circular muscle layer whilst baclofe n exerted a 'GABA-like' contractile effect on the longitudinal muscle layer. Bicuculline (30 mu M) or picrotoxinin (30 mu M) antagonized the GABA- or muscimol-induced relaxations in all preparations and decreas ed the GABA- but not the baclofen-induced contractions of the longitud inal muscle layer. 3 Tetrodotoxin (0.5 mu M) or atropine (0.1 mu M) pr evented the bicuculline-sensitive phases of the GABA or muscimol effec ts on both muscle layers but not the contractile effect of baclofen on the longitudinal muscle layer. 4 The bicuculline-sensitive phases of the GABA effect on both muscle layers were almost completely eliminate d by 1 nM pirenzepine. At this concentration pirenzepine did not affec t the electrically-evoked cholinergic twitch contractions or contracti le responses to applied acetylcholine of both muscle layers. 5 During electrically-evoked cholinergic twitch contractions of both muscle lay ers, GABA (100 mu M) had an inhibitory effect. The inhibition occurred in the presence of pirenzepine (1 nM) but not of bicuculline (30 mu M ). 6 It is suggested that two types of functionally different bicucull ine-sensitive GABA(A) receptors mediate an exitatory presynaptic and a n inhibitory prejunctional action of GABA on the cholinergic transmiss ion in cat terminal ileum.