Characterization of prostanoid relaxant/inhibitory receptors (psi) using a highly selective agonist, TR4979.
TR4979, an analogue of prostaglandin E1 (PGE1) was evaluated on respiratory and non-respiratory isolated tissues known to contain heterogeneous or homogeneous populations of the two classes of prostanoid (prostaglandins and thromboxanes) receptors. These receptors are classified as 'chi' the contractant/stimulant receptor with 'chi 1,2,3' being three subdivisions and 'psi' the relaxant/inhibitory receptor(s). On a respiratory tissue (cat trachea) containing predominantly 'psi'-receptors, TR4979 was 26 times less potent than PGE1 or PGE2. On other respiratory tissues known to contain mixtures of the 'chi 1,2,3'- and 'psi'-receptors (guinea-pig trachea and lung strip, cat lung strip and human bronchial muscle), TR4979 consistently acted as a potent relaxant whereas PGE2 and to a lesser extent PGE1 had significant contractant activities. Human pregnant uterus, guinea-pig and rat pseudo-pregnant uteri, rat colon and fundic strips and chick ileum are known to contain one or more of the three subclasses of the 'chi'-receptor. TR4979 (10(-9) -10(-5) M) was inactive on all these tissues whereas all of the reference prostanoids were contractants of varying potencies. PGE1 and histamine-induced contractions of the guinea-pig isolated ileum were both non-competitively antagonized by increasing concentrations of TR4979 suggesting that 'psi'-receptors also exist on this tissue. TR4979 is a highly selective agonist of prostanoid 'psi' (relaxant/inhibitory)-receptors which at present have been demonstrated to exist mainly in the lung. This prostaglandin analogue is a useful new selective pharmacological tool for revealing as yet unidentified prostanoid 'psi'-receptors and actions in a wide range of non-respiratory tissues/organs such as the guinea-pig ileum.
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002415:Cats; D002645:Chickens; D003106:Colon / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D013189:SRS-A / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D014590:Uterine Contraction / Q000187:drug effects
D011453:Prostaglandins; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D013189:SRS-A; D006632:Histamine; D011433:Propranolol; D000527:Alprostadil; C048491:butaprost; D007213:Indomethacin