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Depressed Patients Have Decreased Binding of Tritiated Imipramine to Platelet Serotonin 'Transporter'

Depressed Patients Have Decreased Binding of Tritiated Imipramine to Platelet Serotonin... Abstract • The high-affinity tritiated (3H) imipramine binding sites are functionally (and perhaps structurally) associated with the presynaptic neuronal and platelet uptake sites for serotonin. Since there is an excellent correlation between the relative potencies of a series of antidepressants in displacing 3H-imipramine from binding sites in human brain and platelet, we have examined the binding of 3H-imipramine to platelets from 14 depressed patients and 28 age- and sex-matched controls. A highly significant decrease in the number of 3H-imipramine binding sites, with no significant change in the apparent affinity constants, was observed in platelets from the depressed patients compared with the controls. These results, coupled with previous studies showing a significant decrease in the maximal uptake of serotonin in platelets from depressed patients, suggest that an inherited or acquired deficiency of the serotonin transport protein or proteins may be involved in the pathogenesis of depression. References 1. Raisman R, Briley M, Langer SZ: Specific tricyclic antidepressant binding sites in rat brain . Nature 1979;281:148-150.Crossref 2. Paul SM, Rehavi M, Skolnick P, et al: Demonstration of specific high affinity binding sites for [3H] imipramine on human platelets . Life Sci 1980;26:953-959.Crossref 3. Briley MS, Raisman R, Langer SZ: Human platelets possess high affinity binding sites for [3H] imipramine . Eur J Pharmacol 1979;58:347-348.Crossref 4. Rehavi M, Paul SM, Skolnick P, et al: Demonstration of specific high affinity binding sites for [3H] imipramine in human brain . Life Sci 1980;26:2273-2279.Crossref 5. Langer SZ, Raisman R, Briley M: Stereoselective inhibition of [3H] imipramine binding by antidepressant drugs and their derivatives . Eur J Pharmacol 1980;64:89-90.Crossref 6. Zis AP, Goodwin FK: Novel antidepressants and the biogenic amine hypothesis of depression: The case for iprindole and mianserin . Arch Gen Psychiatry 1979;36:1097-1107.Crossref 7. Paul SM, Rehavi M, Rice K, et al: Does high affinity [3H] imipramine binding label serotonin reuptake sites in brain and platelet? Life Sci 1981;28:2253-2260.Crossref 8. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria: Rationale and reliability . Arch Gen Psychiatry 1978;35:773-782.Crossref 9. Stahl SM, Meltzer HY: A kinetic and pharmacologic analysis of 5-hydroxytryptamine transport by human platelets and platelet storage granules: Comparison with central serotonergic neurons . J Pharmacol Exp Ther 1978;205:118-132. 10. Lowry O, Rosebrough N, Farr LA, et al: Protein measurement with the Folin phenol reagent . J Biol Chem 1951;193:265-275. 11. Rehavi M, Ittah Y, Rice KC, et al: 2-Nitroimipramine: A selective irreversible inhibitor of [3H] serotonin uptake and [3H] imipramine binding in platelets . Biochem Biophys Res Commun 1981;99:954-959.Crossref 12. Briley MS, Langer SZ, Raisman R, et al: Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients . Science 1980;209:303-305.Crossref 13. Tuomisto J, Tukiainen E: Decreased uptake of 5-hydroxytryptamine in blood platelets from depressed patients . Nature 1976;262:596-598.Crossref 14. Hallstrom C, Pare OS, Ress MB, et al: Platelet uptake of 5-hydroxytryptamine and dopamine in depression . Postgrad Med J 1976;52( (suppl) ):40-44.Crossref 15. Coppen A, Swade C, Wood K: Platelet 5-hydroxytryptamine accumulation in depressive illness . Clin Chim Acta 1978;87:165-168.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Depressed Patients Have Decreased Binding of Tritiated Imipramine to Platelet Serotonin 'Transporter'

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References (15)

Publisher
American Medical Association
Copyright
Copyright © 1981 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1981.01780370017001
Publisher site
See Article on Publisher Site

Abstract

Abstract • The high-affinity tritiated (3H) imipramine binding sites are functionally (and perhaps structurally) associated with the presynaptic neuronal and platelet uptake sites for serotonin. Since there is an excellent correlation between the relative potencies of a series of antidepressants in displacing 3H-imipramine from binding sites in human brain and platelet, we have examined the binding of 3H-imipramine to platelets from 14 depressed patients and 28 age- and sex-matched controls. A highly significant decrease in the number of 3H-imipramine binding sites, with no significant change in the apparent affinity constants, was observed in platelets from the depressed patients compared with the controls. These results, coupled with previous studies showing a significant decrease in the maximal uptake of serotonin in platelets from depressed patients, suggest that an inherited or acquired deficiency of the serotonin transport protein or proteins may be involved in the pathogenesis of depression. References 1. Raisman R, Briley M, Langer SZ: Specific tricyclic antidepressant binding sites in rat brain . Nature 1979;281:148-150.Crossref 2. Paul SM, Rehavi M, Skolnick P, et al: Demonstration of specific high affinity binding sites for [3H] imipramine on human platelets . Life Sci 1980;26:953-959.Crossref 3. Briley MS, Raisman R, Langer SZ: Human platelets possess high affinity binding sites for [3H] imipramine . Eur J Pharmacol 1979;58:347-348.Crossref 4. Rehavi M, Paul SM, Skolnick P, et al: Demonstration of specific high affinity binding sites for [3H] imipramine in human brain . Life Sci 1980;26:2273-2279.Crossref 5. Langer SZ, Raisman R, Briley M: Stereoselective inhibition of [3H] imipramine binding by antidepressant drugs and their derivatives . Eur J Pharmacol 1980;64:89-90.Crossref 6. Zis AP, Goodwin FK: Novel antidepressants and the biogenic amine hypothesis of depression: The case for iprindole and mianserin . Arch Gen Psychiatry 1979;36:1097-1107.Crossref 7. Paul SM, Rehavi M, Rice K, et al: Does high affinity [3H] imipramine binding label serotonin reuptake sites in brain and platelet? Life Sci 1981;28:2253-2260.Crossref 8. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria: Rationale and reliability . Arch Gen Psychiatry 1978;35:773-782.Crossref 9. Stahl SM, Meltzer HY: A kinetic and pharmacologic analysis of 5-hydroxytryptamine transport by human platelets and platelet storage granules: Comparison with central serotonergic neurons . J Pharmacol Exp Ther 1978;205:118-132. 10. Lowry O, Rosebrough N, Farr LA, et al: Protein measurement with the Folin phenol reagent . J Biol Chem 1951;193:265-275. 11. Rehavi M, Ittah Y, Rice KC, et al: 2-Nitroimipramine: A selective irreversible inhibitor of [3H] serotonin uptake and [3H] imipramine binding in platelets . Biochem Biophys Res Commun 1981;99:954-959.Crossref 12. Briley MS, Langer SZ, Raisman R, et al: Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients . Science 1980;209:303-305.Crossref 13. Tuomisto J, Tukiainen E: Decreased uptake of 5-hydroxytryptamine in blood platelets from depressed patients . Nature 1976;262:596-598.Crossref 14. Hallstrom C, Pare OS, Ress MB, et al: Platelet uptake of 5-hydroxytryptamine and dopamine in depression . Postgrad Med J 1976;52( (suppl) ):40-44.Crossref 15. Coppen A, Swade C, Wood K: Platelet 5-hydroxytryptamine accumulation in depressive illness . Clin Chim Acta 1978;87:165-168.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Dec 1, 1981

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