Effects of lithium ion on the inhibitory GTP-binding protein and its coupling response.
Addition of lithium ion to the inhibitory GTP-binding (Gi) protein resulted in a decrease of its ADP-ribosylation by islet-activating protein (pertussis toxin, IAP). The possibility that this decrease was due to dissociation of the Gi protein trimer was examined. Results showed that lithium ions had no appreciable effect on either the Gi protein trimer or its dissociation into its three subunits induced by Mg2+ and GTP gamma S. Next, the effect of lithium ions on Gi protein-mediated adenylate cyclase inhibition and alpha 2-adrenoceptor in human platelet membranes was examined. Lithium ion was found to impair adenylate cyclase inhibition of alpha 2-adrenoceptor stimulation of forskolin-stimulated enzyme activities. The monovalent ion also abolished guanine nucleotide modulation (GTP shift) of agonist binding, while it had no remarkable effects on antagonist binding in alpha 2-adrenoceptor of human platelet membranes. These results suggested that lithium ion caused functional change of the Gi protein without remarkable change of its dissociation, causing modulation in a coupling between alpha 2-adrenoceptor and Gi protein.
Watanabe
Y
Y
Department of Pharmacology I, Osaka University, School of Medicine, Japan.
Kawamoto
H
H
Imaizumi
T
T
Sakagoshi
N
N
Iwakura
K
K
Morita
H
H
Iwasaki
T
T
Yoshida
H
H
D000244:Adenosine Diphosphate / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D037342:Pertussis Toxin; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D012266:Ribose / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000244:Adenosine Diphosphate; D012266:Ribose; D008094:Lithium; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008274:Magnesium