Article |

Guanine Nucleotide-Binding Proteins in Bipolar Affective Disorder:  Effects of Long-term Lithium Treatment

Husseini K. Manji, MD, FRCPC; Guang Chen, MD; Hady Shimon; John K. Hsiao, MD; William Z. Potter, MD, PhD; Robert H. Belmaker, MD
Arch Gen Psychiatry. 1995;52(2):135-144. doi:10.1001/archpsyc.1995.03950140053007.
Text Size: A A A
Published online

Background:  This study examines recent suggestions from a number of investigators that signal-transducing guanine nucleotide-binding (G) proteins may be involved in the pathophysiology of bipolar affective disorder and may represent molecular targets for lithium's mood-stabilizing actions.

Methods:  We used selective antibodies to quantitate the levels of the G protein α subunits that regulate adenylate cyclase activity (Gαs and Gαi2) and phosphoinositide turnover (Gαq/11). We also quantitated levels of pertussis toxin—catalyzed phosphate 32—labeled adenosine diphosphate ([32P] ADP) ribosylation in platelet and leukocyte membranes from a group of 14 untreated (predominantly manic) patients with bipolar affective disorder, 20 lithium-treated euthymic patients with bipolar affective disorder, and 11 healthy controls.

Results:  In both tissues, the immunolabeling of the 45-kd form of Gαs was higher in the bipolar affective disorder group considered as a whole (treated or untreated) compared with controls, effects that reached statistical significance in the leukocyte membranes. There were no significant differences in the immunolabeling of Gαi2/2, Gαq/11, or pertussis toxin—catalyzed [32P]ADP ribosylation in either tissue in the untreated bipolar affective disorder group compared with controls. In both tissues, lithium-treated subjects demonstrated lower levels of Gαq/11 and higher levels of pertussis toxin—catalyzed [32P]ADP-ribosylation, which reached significance in the platelet membranes.

Conclusions:  Our results are complementary to the previously reported findings of elevated Gαs levels in postmortem brain tissue from patients with bipolar affective disorder and in mononuclear leukocytes obtained from depressed patients with bipolar (but not unipolar) affective disorder. The significantly higher levels of pertussis toxin—catalyzed [32P] ADP ribosylation in the subjects receiving long-term lithium-treatment replicates our findings in rat cortex and in healthy volunteers and adds to the growing body of evidence implicating Gαi as a target of lithium's actions.


Sign In to Access Full Content

Don't have Access?

Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more

Subscribe for full-text access to content from 1998 forward and a host of useful features

Activate your current subscription (AMA members and current subscribers)

Purchase Online Access to this article for 24 hours





Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

Related Content

Customize your page view by dragging & repositioning the boxes below.