Differential cAMP levels and serotonin effects in blood peripheral mononuclear cells and lymphocytes from major depression patients.
cAMP regulates immune responses, and modifications in cAMP signaling are involved in the pathophysiology and treatment of depression. In the present report, basal and forskolin-stimulated levels of cAMP were determined in mononuclear cells and lymphocytes from control individuals and major depression patients. Twenty-eight patients between 24 and 59 years old were diagnosed for a major depression episode according to the criteria of the Structural Clinical Interview for Disorders of Axis I of the American Psychiatric Association. These patients presented a score of 25 for severity as measured by Hamilton Rating Scale of Depression (HAM-D), and 23 for Beck Inventory of Depression (BID). Control and patient mononuclear cells were isolated by Ficoll/Hypaque gradients and their lymphocytes were separated from the total mononuclear population by differential adhesion to plastic surface. The basal concentration of cAMP was 50% lower in mononuclear cells and lymphocytes from the depressed patients compared with the control subjects. The response to forskolin was significantly smaller in lymphocytes of major depression patients than in the controls, but no difference was evident in the mononuclear cell preparations. There was a significant increase in cAMP produced by 5HT in mononuclear cells from the control group, but not in their lymphocytes. This effect on mononuclear cells was reduced by the antagonist of 5HT1A receptors, WAY-100,135. However, the simultaneous addition of a specific agonist of 5HT1A receptors, 8-hydroxy-(dipropylamino)tetralin (DPAT) and WAY-100,135 resulted in higher levels of cAMP than with the agonist alone. This effect probably indicates the blockade of 5HT1A receptors and action of 5HT1A agonist on the other subtypes of serotonin receptors expressed on human lymphocytes. This response was not observed in the patient's lymphocytes. In lymphocytes from major depression patients, serotonin and 8-hydroxy-(dipropylamino)tetralin significantly increased cAmp levels, which was slightly reduced by WAY-100,135. The present report indicates: (1) differential responses of immune cells from control individuals and depressed patients, with lower apparent adenylate cyclase activity in patient's cells; (2) variation in the population of cells, with responses to serotonergic agonists being lower in mononuclear cells and higher in lymphocytes from major depression patients; (3) increases of cAMP levels by serotonin and 5HT1A agonist in the patient's cells; and (4) evidence of impairment in serotonergic transduction systems in immune cells during depression.
Mizrahi
C
C
Hospital Centro de Salud Mental del Este, Caracas, Venezuela.
Stojanovic
A
A
Urbina
M
M
Carreira
I
I
Lima
L
L
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000328:Adult; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood*; D003865:Major Depressive Disorder / Q000097:blood*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010879:Piperazines / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology
D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; C081293:WAY 100135; D005576:Colforsin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000242:Cyclic AMP; D009638:Norepinephrine