Platelet membrane alpha 2-adrenergic receptors in depression.
The platelet membrane was used as a model system to examine alpha 2-adrenergic receptors in 30 depressed patients and 30 healthy control subjects. The number of binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were assayed in the same sample. A decreased agonist-receptor affinity was found in depressed patients, whereas receptor density was not significantly altered compared with that in control subjects. In bipolar depressed and dysthymic patients, there was a tendency toward a higher density of alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent depressed subjects. Moreover, a positive correlation between Bmax and Kd values was observed in patients but not in control subjects--a finding that suggests that a compensatory phenomenon occurs in depression. After the patients were treated with antidepressant drugs, an increased affinity (decrease in Kd) was observed, together with a decrease in binding sites. Plasma magnesium concentrations were higher in drug-free depressed patients than in control subjects. In addition, magnesium concentrations were negatively correlated with the density of alpha 2-adrenergic receptor binding sites in depressed patients, both before and during treatment. Lastly, a trend toward a negative correlation between plasma MHPG concentration and the number of binding sites was also observed. These results suggest a complex multifactorial regulation of alpha 2-adrenergic receptors, which are probably hyposensitive in depressive syndromes.
Division of Biochemistry, Institutions Universitaires de Psychiatrie, Geneva Medical School, Switzerland.
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F
Karege
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Bovier
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Widmer
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JM
Gaillard
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Tissot
D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics*; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D003866:Depressive Disorder / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008274:Magnesium / Q000097:blood; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D011810:Quinoxalines / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000928:Antidepressive Agents; D011810:Quinoxalines; D011941:Receptors, Adrenergic; D000068438:Brimonidine Tartrate; D008734:Methoxyhydroxyphenylglycol; D008274:Magnesium