Guanine nucleotide sensitivity of [3H]iloprost binding to prostacyclin receptors.
A component of the displaceable binding of the stable prostacyclin analogue, [3H]iloprost, to membranes from human platelets and the somatic hybrid cell lines NG108-15 and NCB20, was inhibited by guanine nucleotides. The order of potency of a range of nucleotides for this effect was GTP gamma S greater than GppNHp greater than GTP greater than GDP = GMP; ATP, UTP and CTP were ineffective at concentrations up to 1 mM. In the presence of 100 microM GppNHp, iloprost binding curves were displaced to the right of curves obtained in the absence of guanine nucleotide, and their Hill slopes were greater. This was consistent with a conversion of a minor population of high affinity agonist binding sites to lower affinity sites in the presence of guanine nucleotides. These effects of guanine nucleotides on the binding of the agonist ligand [3H]iloprost were consistent with an interaction with a G protein coupled receptor.
Keen
M
M
Department of Pharmacology, Medical School, University of Birmingham, U.K.
Kelly
E
E
MacDermot
J
J
D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006150:Guanine Nucleotides / Q000494:pharmacology*; D016285:Iloprost / Q000378:metabolism*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D014316:Tritium
D006150:Guanine Nucleotides; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D014316:Tritium; D016285:Iloprost