Agonists can discriminate between cloned human and mouse prostacyclin receptors

• Published in: Prostaglandins, leukotrienes and essential fatty acids Vol. 70; no. 5; pp. 423 - 429
• Main Authors: Chow, K.B.S., Jones, R.L., Wise, H.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.05.2004; Elsevier
• Subjects: Adenylyl Cyclases - metabolism; Animals; Biological and medical sciences; Cell receptors; Cell structures and functions; Cloning, Molecular; COS Cells; Cricetinae; Enzyme Activation - drug effects; Epoprostenol - analogs & derivatives; Epoprostenol - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Humans; Iloprost - pharmacology; IP receptors; Mice; Molecular and cellular biology; Prostacyclin; Prostaglandins, Synthetic - pharmacology; Rats; Receptors, Epoprostenol; Receptors, Prostaglandin - agonists; Receptors, Prostaglandin - genetics; Recombinant Proteins - agonists; Recombinant Proteins - genetics; Signal Transduction - drug effects; Species Specificity; Taprostene; Type C Phospholipases - metabolism; Vertebrates: endocrinology; Prostacyclin; Taprostene; IP receptors; Human; Vertebrata; Agonist; Specificity; Mammalia; Prostaglandin I2; Mouse; Animal; Rodentia; Biological receptor
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/j.plefa.2003.08.022

The ability of prostacyclin analogues to stimulate adenylyl cyclase (AC) and phospholipase C (PLC) in Chinese hamster ovary (CHO) cells expressing cloned human (hIP) or cloned mouse (mIP) prostacyclin receptors has been compared. For hIP, the order of potency (pEC 50) for stimulating AC and PLC pathways was similar: AFP-07 (9.3, 8.4)>cicaprost (8.3, 6.9), iloprost (7.9, 6.8)>taprostene (7.4, 6.8)>carbacyclin (6.9, 6.6), PGE 1 (6.6, 5.1). Although the standard IP agonists cicaprost and iloprost behaved similarly in both hIP and mIP receptor-expressing cells, carbacyclin and PGE 1 showed significantly higher potency at the mIP receptor, suggesting that the agonist recognition sites on hIP and mIP receptors are not identical. A further distinction between hIP and mIP receptors was found with taprostene, which had greater efficacy at hIP receptors (AC 94%, PLC 14%) than at mIP receptors (AC 77%, PLC 0%) (cicaprost=100% in each assay).