Biochemical and functional evidence of supersensitive platelet alpha 2-adrenoceptors in major affective disorder. Effect of long-term lithium carbonate treatment.
The hypothesis that depressive illness is related to supersensitive alpha 2-adrenoceptors in the brain has been tested indirectly in blood platelets. The binding of tritiated clonidine hydrochloride to platelet membranes, a ligand that labels only the high-affinity state of the alpha 2-adrenoceptor that is coupled with cell functions, and the aggregation response induced by epinephrine hydrochloride, which is the result of the activation of the high-affinity state, were measured and correlated in 13 patients with major affective disorder. Both the number of high-affinity binding sites and the aggregation response were increased in depressed patients. There was a negative and significant correlation between both measures in the same depressed patients. Treatment with lithium carbonate (Plenur [Spain]; Linthane, comparable US product) was associated with a decrease in the high-affinity state and with an increase in the aggregation response. Thus, major effective disorder may be related to a dysfunction of the high-affinity state of the alpha 2-adrenoceptor that recognizes agonists and mediates physiological effects.
D000328:Adult; D003000:Clonidine / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008094:Lithium / Q000494:pharmacology; D016651:Lithium Carbonate; D008297:Male; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014316:Tritium
D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D016651:Lithium Carbonate; D008094:Lithium; D003000:Clonidine; D004837:Epinephrine