Receptor-mediated and receptor-independent activation of G-proteins in rat brain membranes.
High-affinity GTPase activity intrinsic to G-proteins, which serves as an index of G-protein activation elicited through agonist-stimulated receptors as well as by receptor-independent direct G-protein activators like mastoparan, was measured in rat brain membranes. Receptor-mediated high-affinity GTPase activity was detectable preferentially for the Gi subfamily associated with adenylyl cyclase inhibition mediated by group II metabotropic glutamate, pirenzepine-insensitive muscarinic acetylcholine, GABA(B), adenosine A1, dopamine D2-like (striatum), and serotonin 5-HT1A (hippocampus) receptors. The pharmacological characteristics of such receptor-mediated high-affinity GTPase activities were presented. Mastoparan, a tetradecapeptide from wasp venom which has been shown to directly activate Gi and Go, inhibited low-affinity GTP hydrolyzing activity, probably due to its activating effect on nucleoside diphosphokinase (NDPK). When NDPK activity was inhibited completely by UDP, mastoparan stimulated high-affinity GTPase activity in a concentration-dependent manner. There are many compounds other than mastoparan with apparently diverse structural properties which have been shown to directly activate G-proteins. The relevance and possible participation of receptor-independent mode of G-protein activation for some neuropeptides were discussed.
Odagaki
Y
Y
Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan.
Nishi
N
N
Koyama
T
T
D000818:Animals; D001921:Brain / Q000502:physiology* / Q000648:ultrastructure; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008566:Membranes / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*
D011956:Receptors, Cell Surface; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins