title: Characterization of endothelin receptors mediating mechanical responses to the endothelins in the isolated stomach strip of the rat.
abstract: We have characterized the receptors mediating the mechanical responses of the isolated stomach strip to endothelin-1 (ET-1), endothelin-3 (ET-3) and the ETB-selective receptor agonists sarafotoxin 6c (SX6c) and IRL 1620. As antagonists we used BQ-123 (ETA receptor selective), BQ-788 (ETB receptor selective) and PD 145065 (ETA/ETB receptor nonselective). We have also compared the responses of the mature peptides to their precursors human big ET-1(1-38), porcine big ET-1(1-39) and big ET-3(1-41) amide. ET-1, ET-3, SX6c and IRL 1620 produced equipotent concentration-dependent contractions of the rat stomach strips that were antagonized by PD 145065 (10(-5) M) or BQ-788 (10(-5) M) but not by BQ-123 (10-5 M). This indicates that the ETB receptor mediates contractions to the endothelins in this preparation. In preparations precontracted with PGE2 (3 x 10(-8) M), ET-1, but not SX6c (both 3 x 10(-9) M), caused a transient (< 2 min) relaxation (approx. 40% of the induced tone). This relaxation was antagonized by BQ-123 (10(-5) M) but prolonged by BQ-788, and therefore mediated by ETA receptors. A single administration of 3 x 10(-7) M ET-1, ET-3, SX6c or IRL 1620 produced contractions that reached a maximal response after 1 to 3 min. The contractions were not maintained, although responses to ET-1 or ET-3 lost their tone less rapidly than those to SX6c or IRL 1620.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
authors.forename: G H
authors.initials: GH
authors.lastname: Allcock
authors.forename: B
authors.initials: B
authors.lastname: Battistini
authors.forename: A
authors.initials: A
authors.lastname: Fournier
authors.forename: T D
authors.initials: TD
authors.lastname: Warner
authors.forename: J R
authors.initials: JR
authors.lastname: Vane
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008666:Metalloendopeptidases; D009119:Muscle Contraction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D013270:Stomach / Q000187:drug effects* / Q000502:physiology*; D013552:Swine
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D016232:Endothelins; D010446:Peptide Fragments; D011498:Protein Precursors; D017466:Receptors, Endothelin; C096169:endothelin-3 (1-41)amide; D011189:Potassium Chloride; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D015232:Dinoprostone