The effect of iloprost on the ADP-ribosylation of Gs alpha (the alpha-subunit of Gs).
Treatment of platelets with a prostacyclin analogue, iloprost, decreased the cholera-toxin-induced ADP-ribosylation of membrane-bound Gs alpha (alpha-subunit of G-protein that stimulates adenylate cyclase; 42 kDa protein) and a cytosolic substrate (44 kDa protein) [Molina y Vedia, Reep & Lapetina (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 5899-5902]. This decrease is apparently not correlated with a significant change in the quantity of membrane Gs alpha, as detected by two Gs alpha-specific antisera. This finding contrasts with the suggestion in a previous report [Edwards, MacDermot & Wilkins (1987) Br. J. Pharmacol. 90, 501-510], indicating that iloprost caused a loss of Gs alpha from the membrane. Our evidence points to a modification in the ability of the 42 kDa protein to be ADP-ribosylated by cholera toxin. This modification of Gs alpha might be related to its ADP-ribosylation by endogenous ADP-ribosyltransferase activity. Here we present evidence showing that Gs alpha was ADP-ribosylated in platelets that had been electropermeabilized and incubated with [alpha-32P]NAD+. This endogenous ADP-ribosylation of Gs alpha is inhibited by nicotinamide and stimulated by iloprost.
Molina y Vedia
L
L
Division of Cell Biology, Burroughs Wellcome Co., Research Triangle Park, NC 27709.
Nolan
R D
RD
Lapetina
E G
EG
D000244:Adenosine Diphosphate / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability; D002772:Cholera Toxin; D011464:Epoprostenol / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000097:blood*; D006801:Humans; D016285:Iloprost; D011065:Poly(ADP-ribose) Polymerases / Q000097:blood
D000244:Adenosine Diphosphate; D002772:Cholera Toxin; D011464:Epoprostenol; D011065:Poly(ADP-ribose) Polymerases; D019204:GTP-Binding Proteins; D016285:Iloprost