Hyperfunctional G proteins in mononuclear leukocytes of patients with mania.
In a recent study, we found that lithium inhibits the function of guanine nucleotide-binding proteins, implicating G proteins as the common site for both the antimanic and antidepressant therapeutic effects of lithium. These findings may also suggest that an altered G protein function is of pathophysiological importance in bipolar affective disorder. In the present study, the coupling of both muscarinic-cholinergic receptors and beta-adrenergic receptors to pertussis toxin-sensitive G proteins or cholera toxin-sensitive G proteins was compared among untreated manic patients, lithium-treated euthymic bipolar patients, and healthy volunteers using mononuclear leukocyte (MNL) membrane preparations. Hyperactive function of G proteins was detected in untreated manic patients. Both isoproterenol-induced and carbamylcholine-induced increases in Gpp(NH)p binding capacity were twofold to threefold higher than the increases observed in healthy volunteers. On the other hand, lithium-treated euthymic bipolar patients showed G protein responses to agonist activation that were no different from the healthy volunteers. Altered G protein function may be of pathophysiological importance in bipolar affective disorder.
Schreiber
G
G
Beer Sheva Mental Health Centre, Ida and Solomon Stern Psychiatry Research Unit, Ben Gurion University, Israel.
Avissar
S
S
Danon
A
A
Belmaker
R H
RH
D000244:Adenosine Diphosphate / Q000378:metabolism; D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D006165:Guanylyl Imidodiphosphate / Q000493:pharmacokinetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
D006165:Guanylyl Imidodiphosphate; D000244:Adenosine Diphosphate; D008094:Lithium; D019204:GTP-Binding Proteins