Lack of interfering effects of lithium on receptor/G protein coupling in human platelet and rat brain membranes.
To verify the theory that lithium exerts its multiple effects by altering the receptor-mediated G protein's activation, in vitro effects of lithium on agonist-induced guanosine triphosphate (GTP) hydrolysis were examined. The basal GTP hydrolyzing activity in human platelet membranes was decreased nonselectively by either LiCl or NaCl at millimolar concentrations, whereas (-)-epinephrine-stimulated increase in the activity (an index of alpha (2A)-adrenoceptor coupled Gi2 function) was unaltered. Furthermore, the stimulation of high-affinity GTPase activity induced by dopamine, carbachol, and R-N(6)-phenylisopropyladenosine in rat brain membranes (indices of the functional coupling between dopamine D2-like, pirenzepine-insensitive muscarinic, and adenosine A1 receptors and their respective Gi proteins) was substantially unaltered regardless of whether 0.5 mmol/L adenosine 5'-(beta, gamma-imido)triphosphate (i.e., 1.75 mmol/L lithium) was included in the assay mixture or not. These results indicate that lithium does not affect in vitro the receptor-mediated activational process of G proteins, at least not of Gi associated with adenylate cyclase inhibition.
Odagaki
Y
Y
Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan.
Nishi
N
N
Koyama
T
T
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled; D013570:Synaptic Membranes / Q000187:drug effects
D018692:Antimanic Agents; C097350:GPR12 protein, human; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D018021:Lithium Chloride