Factors affecting prostacyclin receptor agonist efficacy in different cell types
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AbstractOctimibate and related nonprostanoid prostacyclin mimetics are partial agonists displaying highly tissue-specific responses. Octimibate demonstrated considerably greater efficacy for stimulation of adenylyl cyclase activity in Chinese hamster ovary cells transiently expressing mouse prostacyclin receptors (mIP-CHO cells) when compared to human SK-N-SH neuroblastoma cells, which endogenously express prostacyclin (IP) receptors. Pretreatment of both cell types with pertussis toxin (PTx) failed to influence IF agonist efficacy or potency, indicating a lack of involvement of an agonist-stimulated inhibitory G(i)-coupled pathway. Although stimulation of mIP-CHO cells with the full agonist cicaprost increased both [H-3]Cyclic AMP and [H-3]inositol phosphate ([H-3]IP) accumulation (pEC(50) values of 8.35 and 6.82, respectively), IP receptor signalling through G(q) in SK-N-SH cells was absent. Inhibition of protein kinase C (PKC) in mIP-CHO cells increased [H-3]IP accumulation but had no effect on [H-3]cyclic AMP accumulation. Therefore, the poor coupling of the IP receptor in SK-N-SH cells to G(q) is unlikely to explain the relatively low efficacy of octimibate for stimulating adenylyl cyclase in these cells. Furthermore, protein kinase A (PKA) inhibition appears to enhance IP receptor signalling through both G(s) and G(q) in mIP-CHO cells. (C) 2001 Elsevier Science Inc. All rights reserved.
All Author(s) ListKam YW, Chow KBS, Wise H
Journal nameCellular Signalling
Volume Number13
Issue Number11
Pages841 - 847
LanguagesEnglish-United Kingdom
KeywordsIP receptor; neuroblastoma cells; partial agonists; prostacyclin; receptor coupling
Web of Science Subject CategoriesCell Biology; CELL BIOLOGY

Last updated on 2020-01-04 at 03:27