Lack of Interfering Effects of Lithium on Receptor/G Protein Coupling in Human Platelet and Rat Brain Membranes

• Published in: Biological psychiatry (1969) 1997-10, Vol.42 (8), p.697-703
• Main Authors: Odagaki, Yuji, Nishi, Nobuyuki, Koyama, Tsukasa
• Format: Article
• Language: English
• Subjects: Animals; Antimanic Agents - pharmacology; Biological and medical sciences; Blood Platelets - drug effects; Corpus Striatum - drug effects; Culture Techniques; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; G proteins; GTP Phosphohydrolases - metabolism; guanosine triphosphatase; Guanosine Triphosphate - metabolism; Hippocampus - drug effects; Humans; Lithium; Lithium Chloride - pharmacology; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; platelet; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; rat brain; Rats; Rats, Sprague-Dawley; receptor/G protein coupling; Receptors, Cell Surface - drug effects; Receptors, G-Protein-Coupled; Synaptic Membranes - drug effects
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(96)00443-X

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 α 2A-adrenoceptor coupled G i2 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 D 2-like, pirenzepine-insensitive muscarinic, and adenosine A 1 receptors and their respective G i proteins) was substantially unaltered regardless of whether 0.5 mmol/L adenosine 5′-(β, γ-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 G i associated with adenylate cyclase inhibition.