We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
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

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?





Also 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.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
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.


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

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

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