Endothelin Receptors in Gastrointestinal Smooth Muscle

Abstract

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, ET(A) and ET(B), have been cloned. ET(A) receptors have higher affinities for ET-1 and ET-2 than ET-3, while ET(B) 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 ET(A) receptors, ET(B) receptors or both ET(A) and ET(B) receptors, depending on the tissues and species. In addition to contraction, ET causes smooth muscle relaxation through interaction with ET(A) receptors or ET(B) receptors. At the present time, there are no studies showing that ET causes smooth muscle relaxation through interaction with both ET(A) and ET(B) 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.

Endothelin receptors: what's new and what do we need to know?

“…Implication here means that synthetic machinery for ET peptides, ET peptides themselves, and ET receptors have been localized to tissues in these systems, as well as demonstration that ET-1 causes a physiological function within that system. An incomplete list includes the cardiovascular (11,12,16,98), renal (35,58,87), central nervous (103), gastrointestinal (45), pituitary (61), adrenal (24,43,95,96), nasal (83), peripheral nervous (20,33,82), immune (76), hepatic (70), genitourinary (15), and endocrine systems (75).…”

Relaxant effect of <i>Lagenaria breviflora</i> Roberty fruit pulp and seeds on isolated rabbit ileum

“…These fruit extracts may also interact with other non-adrenergic receptors that cause relaxation of the gastrointestinal (GI) smooth muscle, but were not included in this study. A family of peptides known as endothelins (ET) cause smooth muscle relaxation in the oesophagus, stomach and ileum through interaction with ET(A) or ET(B) receptors (Huang, 2005). Neurotransmitters such as adenosine, adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP) and other derivatives of these neurotransmitters, and nitric oxide are known to cause GI smooth muscle relaxation by stimulating purinoceptors (Burnstock, 2001;Giaroni et al, 2005;McDonnell et al, 2008).…”

Endothelin A receptors mediate relaxation of guinea pig internal anal sphincter through cGMP pathway

“…Three isopeptides of ET, i.e., ET‐1, ET‐2, and ET‐3, have been identified. Endothelins act on cardiovascular, gastrointestinal, tracheal, urinary, and uterine smooth muscle 1,2 . In the gastrointestinal system, ET causes contraction or relaxation of the esophagus, lower esophageal sphincter, stomach, gallbladder, common bile duct, intestines, and internal anal sphincter 1–11 .…”

“…Endothelins act on cardiovascular, gastrointestinal, tracheal, urinary, and uterine smooth muscle 1,2 . In the gastrointestinal system, ET causes contraction or relaxation of the esophagus, lower esophageal sphincter, stomach, gallbladder, common bile duct, intestines, and internal anal sphincter 1–11 . Previous studies have demonstrated the involvement of ETs in many diseases, including pulmonary arterial hypertension, treatment resistant essential hypertension, proteinuric renal disease, and cancer 1,12–14 .…”

“…In the gastrointestinal system, ET causes smooth muscle contraction through interaction with ET A receptors, ET B receptors or both ET A and ET B receptors. On the other hand, ET causes smooth muscle relaxation through interaction with ET A receptors or ET B receptors 1–11 …”