Localization of Endothelin-1 and Its Binding Sites to the Nervous System of the Human Colon

Endothelin-1 (ET-1) has been reported to possess a wide variety of biological activities, including neurotransmission. Our aim was to demonstrate ET-like immunoreactivity (ET-LI) and its binding sites in human enteric nervous system using immunohistochemistry and in vitro autoradiography. ET-LI was displayed in nerve bundles and most of the ganglion cells in both myenteric and submucous plexuses, many of which costored VIP. [125I]ET-1 binding sites were identified, especially to plexuses, mucosa, and blood vessels. High-affinity (Kd = 0.35 +/- 0.014 nM; mean +/- SEM) binding sites, with a maximum binding capacity (Bmax) of 92 +/- 6.3 amol/mm2, were demonstrated in the myenteric plexus. This study provides evidence that ET-1 is a neuropeptide in the human colon with binding sites on neural plexuses and mucosa, indicating a possible role in the modulation of motility and secretion in the human intestine.