Pseudopterosin A inhibits phagocytosis and alters intracellular calcium turnover in a pertussis toxin sensitive site in Tetrahymena thermophila.
The free living ciliate Tetrahymena thermophila was chosen as a cellular model in order to investigate the mode of action of the anti-inflammatory marine natural product Pseudopterosin A (PsA). In this paper we present evidence that PsA inhibits phagosome formation (KD=10.5 microM) and triggers a discrete intracellular calcium release (depletion) from a site in T. thermophila cells (KD=6.4 microM). Pre-treatment with the Gi/o protein inhibitor, pertussis toxin (PTX), inhibits PsA activity of both responses providing pharmacological evidence that the site of action for PsA is at a PTX sensitive G protein or a G protein coupled receptor (GPCR). Addition of extracellular calcium induced a concentration dependent increase in the incidence of phagosome formation (KD=30.3 microM) and was blocked by PsA pre-treatment. This particular effect of PsA on extracellular calcium was not blocked by PTX pre-treatment.
Moya
Claudia E
CE
Department of Ecology, Evolution and Marine Biology, University of California, Santa Barbara, Santa Barbara, CA, 93106-9610, USA. moya@lifesci.ucsb.edu
Jacobs
Robert S
RS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D004224:Diterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006027:Glycosides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D010588:Phagosomes / Q000187:drug effects / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology; D016808:Tetrahymena thermophila / Q000187:drug effects
D004224:Diterpenes; D004963:Estrenes; D006027:Glycosides; D011760:Pyrrolidinones; C049922:pseudopterosins; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002122:Calcium Chloride; D002118:Calcium