Characterization of prostanoid relaxant/inhibitory receptors (ψ) using a highly selective agonist, TR4979

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Abstract
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 ‘χ’ the contractant/stimulant receptor with ‘χ1,2,3’ being three subdivisions and ‘ψ’ the relaxant/inhibitory receptor(s). On a respiratory tissue (cat trachea) containing predominantly ‘ψ’‐receptors, TR4979 was 26 times less potent than PGE1 or PGE2. On other respiratory tissues known to contain mixtures of the ‘χ1,2.3’‐ and ‘ψ’‐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 ‘χ’‐receptor. TR4979 (10−9 − 10−5 M) was inactive on all these tissues whereas all of the reference prostanoids were contractants of varying potencies. PGE, and histamine‐induced contractions of the guinea‐pig isolated ileum were both noncompetitively antagonized by increasing concentrations of TR4979 suggesting that ‘ψ’‐receptors also exist on this tissue. TR4979 is a highly selective agonist of prostanoid ‘ψ’ (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 ‘ψ’‐receptors and actions in a wide range of non‐respiratory tissues/organs such as the guinea‐pig ileum.