The generation of inositolglycan mediators from rat liver plasma membranes: the role of guanine nucleotide binding proteins.
The guanine nucleotide dependence for the generation of inositolglycan second messengers from rat liver plasma membranes has been investigated. Plasma membranes, when treated with insulin release a soluble mediator substance which activates pyruvate dehydrogenase (PDH). Guanosine 5'-[3-thio]triphosphate (GTP gamma S) was found to be as potent as insulin in stimulating mediator release. The stimulatory effects of GTP gamma S required the presence of magnesium and following preincubation of membranes with guanosine 5'-[2-thio]diphosphate (GDP beta S) the stimulation of mediator release by either insulin or GTP gamma S was blocked. The activation of PDH by mediator fractions produced in response to either insulin or GTP gamma S was abolished following treatment of the fractions with anti-inositolglycan antibodies. The significance of these observations with respect to the possible involvement of a regulatory guanine-nucleotide binding protein (G-protein) in the generation of insulin mediators is discussed.
Kilgour
E
E
Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville 22908.
Larner
J
J
Romero
G
G
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D007294:Inositol / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011134:Polysaccharides / Q000276:immunology / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems
D000906:Antibodies; D006150:Guanine Nucleotides; D007328:Insulin; D011134:Polysaccharides; D011768:Pyruvate Dehydrogenase Complex; C068698:inositol-glycan; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007294:Inositol; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins