Endothelin Receptors in Gastrointestinal Smooth Muscle

Endothelins (ETs) are a family of peptides with 21-amino-acid residues. ET-1 was identified as a potent vasoconstrictor produced by vascular endothelial cells. Three distinct isoforms of ET, i.e. ET-1, ET-2 and ET-3, have been found to exist in a variety of tissues. ET was later found to cause contraction as well as relaxation of smooth muscle in many physiologic systems. In the gastrointestinal tract, ET causes contraction and/or relaxation of the esophagus, stomach, ileum and colon. In the hepatobiliary system, ET causes contraction of the portal vein, hepatic stellate cells, gallbladder and common bile duct. In mammalian species, two classes of ET receptors, ETA and ETB, have been cloned. ETA receptors have higher affinities for ET-1 and ET-2 than ET-3, while ETB receptors have the same affinities for ET-1, ET- 2 and ET-3. In the gastrointestinal system, ET causes smooth muscle contraction through interaction with ETA receptors, ETB receptors or both ETA and ETB receptors, depending on the tissues and species. In addition to contraction, ET causes smooth muscle relaxation through interaction with ETA receptors or ETB receptors. At the present time, there are no studies showing that ET causes smooth muscle relaxation through interaction with both ETA and ETB subtypes. ET induces contraction in most of the non-sphincter muscle except the fundus of the stomach. On the other hand, ET causes relaxation and contraction in the lower esophageal and internal anal sphincters. ET may play an important role in the control of human gastrointestinal motility and portal vein pressure.