THE LEU(13)-MOTILIN (KW-5139)-EVOKED RELEASE OF ACETYLCHOLINE FROM ENTERIC NEURONS IN THE RABBIT DUODENUM

1 Involvement of cholinergic mechanisms in the contractile response to Leu13-motilin (LMT, KW-5139) was investigated in rabbit duodenal segments, and longitudinal muscle-myenteric plexus (LM-MP) preparations preincubated with [H-3]-choline. 2 Contractile response to LMT (0. 1 nm - 1 mum) consisted of an initial rapid (phasic) contraction and a tonic contraction slowly fading to a sustained plateau. LMT caused a concentration-dependent phasic contraction of rabbit isolated duodenal segments. The EC50 value was 2.5nm and the maximum amplitude of the contraction was 103 % of the response induced by acetylcholine (ACh, 100 mum). Neither tetrodotoxin nor atropine changed the EC50 value or the maximum amplitude of the response to LMT. 3 Both atropine and tetrodotoxin decreased the amplitude and accelerated fading of the tonic contraction produced by LMT. 4 LMT (30 nm - 3 mum) induced an increase of H-3-outflow, in a concentration-dependent manner. The LMT-induced increase of H-3-outflow was prevented by removal of external Ca2+ or by the presence of tetrodotoxin. 5 Porcine motilin (I 0 nm - 1 mum) also stimulated the release of H-3 at a similar concentration-range to that seen with LMT. 6 Pretreatment with LMT (3 mum for 20 min) decreased LMT- and the porcine motilin-evoked release of H-3 but did not alter the high K+-evoked release. 7 Our results suggest that LMT and porcine motilin stimulate the release of ACh from enteric neurones through the same receptor, and that the release of ACh plays a role in tonic components of contraction in the rabbit duodenum.