title: Differential effects of suramin on the coupling of receptors to individual species of pertussis-toxin-sensitive guanine-nucleotide-binding proteins.
abstract: The anti-helminthic drug suramin inhibited the basal high-affinity GTPase activity of both C6 BU1 glioma and NG 108-15 neuroblastoma x glioma hybrid-cell membranes with an IC50 (concentration causing half-maximal inhibition) value close to 30 micrograms/ml. This effect was shown to occur via a non-competitive mechanism in which the binding affinity of the G-proteins for GTP was not altered, but the maximal velocity of the subsequent hydrolysis was reduced. In NG 108-15 membranes, both opioid peptides and foetal-calf serum stimulated high-affinity GTPase activity in a pertussis-toxin-sensitive manner. These effects have previously been shown to be mediated by different G-proteins [McKenzie, Kelly, Unson, Spiegel & Milligan (1988) Biochem. J. 249, 653-659]. Suramin completely prevented the opioid-peptide-stimulated increase in GTP hydrolysis, but did not prevent the opioid peptide from binding to its receptor. Suramin, however, did not block the foetal-calf-serum-stimulated GTPase response. This selective action of suramin provides further evidence for distinct roles for two separate pertussis-toxin-sensitive G-proteins in signal transduction in NG 108-15 membranes and provides the first evidence for a selective effect of a drug on the functions of different G-proteins.
authors.affiliation: Department of Pharmacology, University of Glasgow, Scotland, U.K.
authors.forename: S J
authors.initials: SJ
authors.lastname: Butler
authors.forename: E C
authors.initials: EC
authors.lastname: Kelly
authors.forename: F R
authors.initials: FR
authors.lastname: McKenzie
authors.forename: S B
authors.initials: SB
authors.lastname: Guild
authors.forename: M J
authors.initials: MJ
authors.lastname: Wakelam
authors.forename: G
authors.initials: G
authors.lastname: Milligan
mesh_terms: D000818:Animals; D001769:Blood; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors; D019204:GTP-Binding Proteins / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D004743:Enkephalin, Leucine; D013498:Suramin; D016308:Enkephalin, Leucine-2-Alanine; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins