Localization of endothelin ET(B) receptors on the myenteric plexus of guinea-pig ileum and the receptor-mediated release of acetylcholine

1 The type of endothelin (ET) receptor located on the myenteric neurones of guinea-pig ileum was determined by receptor autoradiography and function of the receptor was examined by release experiments of acetylcholine (ACh) from the longitudinal muscle myenteric plexus (LM-MP) preparations. 2 Specific [I-125]-ET-1 binding sites were distributed in muscle layers, myenteric and submucous plexuses, and mucosa layers. High-grain densities were detected in both myenteric and submucous plexuses. 3 Binding in the myenteric plexus was abolished by incubation with either IRL 1620 (endothelin ET(B) receptor agonist) or BQ 788 (endothelin ET(B) receptor antagonist), but not with BQ 123 (endothelin ET(A) receptor antagonist). The [I-125]-IRL 1620 binding sites were evident in the myenteric plexus. Thus, the endothelin receptor located on the myenteric neurones is of the ET(B) type. 4 ET-1 (10(-10)-3x10(-8)M) and ET-3 (10(-10)-3x10(-8)M) evoked H-3 outflow from LM-MP preparations of ileum preloaded with [H-3]-choline, in a concentration-dependent manner. There was no significant difference between maximum amounts of ET-l-evoked and ET-3-evoked H-3 outflow. 5 ET-1 and ET-3 evoked outflow of H-3 was BQ 788-sensitive, but BQ 123-insensitive. Both evoked outflows of H-3 were Ca2+-dependent and tetrodotoxin-sensitive. 6 These results indicate that the endothelin ET(B) receptor is located on the enteric cholinergic neurones and that stimulation evokes the release of ACh.