Abstract
After prolonged exposure to epinephrine, platelets are observed to desensitize α2-adrenoceptor-mediated aggregation responses in vitro. Herein, this phenomenon was studied as a possible in vitro model for α2-urenoceptor dysregulation in depression. Platelet-rich plasmas obtained from 22 unipolar depressed patients and 25 healthy subjects were preincubated with 20 μmol/L of epinephrine for various lengths of time prior to stirring. By comparing the subsequent extents of aggregation, we observed significantly less desensitization at 4, 20, 30, or 60 minutes postepinephrine exposure (p ≤ .05) in depressed patients as compared to healthy controls. This blunted desensitization appeared to be due to a delayed onset of desensitization during the first 0.5 to 2 minutes after epinephrine exposure, since thereafter, the monoexponential desensitization rate did not differ in depressed patients, but the extent of desensitization remained less as compared to healthy subjects. The extent of desensitization was correlated (r = −0.48, p = .02) with the density (Bmax) of the α2-adrenoceptor high-affinity state, as detected in undesensitized platelet membranes by p125I-clonidine-binding. An elevation was also observed in the density of nonadrenergic p125I-clonidine-binding sites (putative imidazoline I1 sites) in platelet membranes from depressed patients compared to healthy control subjects. Following treatment with desipramine, the patients (n = 15) displayed more normal (nonblunted) extents of desensitization of aggregation, and the Bmax values for the putative I1 sites were at the levels of healthy controls. If similar aberrations exist in neurons of depressed patients, this may explain a dysregulation of the noradrenergic system believed to underlie depression.
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Address reprint requests to: John E. Piletz, Ph.D., Department of Psychiatry, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, Ohio 44109-1998.
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Piletz, J., Chikkala, D., Khaitan, L. et al. Delayed Desensitization of α2-Adrenoceptor-Mediated Platelet Aggregation in Depressed Patients. Neuropsychopharmacol 9, 55–66 (1993). https://doi.org/10.1038/npp.1993.43
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DOI: https://doi.org/10.1038/npp.1993.43