Receptor-mediated and receptor-independent activation of G-proteins in rat brain membranes

High-affinity GTPase activity intrinsic too-proteins, which sen es 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 G(i) subfamily associated with adenylyl cyclase inhibition mediated by group II metabotropic glutamate, pirenzepine-insensitive muscarinic acetylcholine, GABA(B), adenosine A(1), dopamine D-2-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 G(i) and G(o), 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.