Agonists can discriminate between cloned human and mouse prostacyclin receptors.
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).
Chow
K B S
KB
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Jones
R L
RL
Wise
H
H
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D051379:Mice; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D051381:Rats; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000235:genetics; D011994:Recombinant Proteins / Q000819:agonists / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D010738:Type C Phospholipases / Q000378:metabolism
C113936:PTGIR protein, human; D011465:Prostaglandins, Synthetic; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D011994:Recombinant Proteins; C039188:taprostene; D011464:Epoprostenol; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D016285:Iloprost; C043867:cicaprost