LOCALIZATION OF ENDOTHELIN ET(B) RECEPTORS ON THE MYENTERIC PLEXUS OFGUINEA-PIG ILEUM AND THE RECEPTOR-MEDIATED RELEASE OF ACETYLCHOLINE

1 The type of endothelin (ET) receptor located on the myenteric neuron es of guinea-pig ileum was determined by receptor autoradiography and function of the receptor was examined by release experiments of acetyl choline (ACh) from the longitudinal muscle myenteric plexus (LM-MP) pr eparations. 2 Specific [I-125]-ET-1 binding sites were distributed in muscle layers, myenteric and submucous plexuses, and mucosa layers. Hi gh-grain densities were detected in both myenteric and submucous plexu ses. 3 Binding in the myenteric plexus was abolished by incubation wit h either IRL 1620 (endothelin ET(B) receptor agonist) or BQ 788 (endot helin ET(B) receptor antagonist), but not with BQ 123 (endothelin ET(A ) receptor antagonist). The [I-125]-IRL 1620 binding sites were eviden t in the myenteric plexus. Thus, the endothelin receptor located on th e 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 preparation s 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 outfl ow of H-3 was BQ 788-sensitive, but BQ 123-insensitive. Both evoked ou tflows 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 o f ACh.