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Biochemical and Functional Evidence of Supersensitive Platelet α2-Adrenoceptors in Major Affective Disorder: Effect of Long-term Lithium Carbonate Treatment

Biochemical and Functional Evidence of Supersensitive Platelet α2-Adrenoceptors in Major... Abstract • The hypothesis that depressive illness is related to supersensitive α2-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 α2-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 affective disorder may be related to a dysfunction of the high-affinity state of the α2-adrenoceptor that recognizes agonists and mediates physiological effects. References 1. Charney DS, Menkes DB, Heninger GR: Receptor sensitivity and the mechanism of action of antidepressant treatment: Implications for the etiology and therapy of depression . Arch Gen Psychiatry 1981;38:1160-1180.Crossref 2. Cohen RM, Campbell IC, Cohen MR, Torda T, Pickar D, Siever LJ, Murphy DL: Presynaptic noradrenergic regulation during depression and antidepressant drug treatment . Psychiatr Res 1980;3:93-105.Crossref 3. Garcia-Sevilla JA, Zis AP, Hollingsworth PJ, Greden JF, Smith CB: Platelet α2-adrenergic receptors in major depressive disorder: Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment . Arch Gen Psychiatry 1981;38:1327-1333.Crossref 4. Smith CB, Garcia-Sevilla JA: α2-Adrenoreceptors in endogenous depression , in Langer SZ, Takanashi R, Segawa T, Briley M (eds): Advances in the Biosciences . New York, Pergamon Press, 1982, vol 40: New Vistas in Depression, pp 99-106. 5. Langer SZ: Presynaptic regulation of the release of catecholamines . Pharmacol Rev 1981;32:337-362. 6. Starke K: Presynaptic receptors . Annu Rev Pharmacol Toxicol 1981;21:7-30.Crossref 7. Bunney WE Jr, Davis JM: Norepinephrine in depressive reactions: A review . Arch Gen Psychiatry 1965;13:483-494.Crossref 8. Schildkraut JJ: The catecholamine hypothesis of affective disorders: A review of supporting evidence . Am J Psychiatry 1965;122:509-522. 9. Smith CB, García-Sevilla JA, Hollingsworth PJ: α2-Adrenoceptors in rat brain are decreased after long-term tricyclic antidepressant drug treatment . Brain Res 1981;210:413-418.Crossref 10. Pile A, Vetulani J: Attenuation by chronic imipramine treatment of 3H-clonidine binding to cortical membranes and of clonidine-induced hypothermia: The influence of central chemosympathectomy . Brain Res 1982;238:499-504.Crossref 11. Cohen RM, Campbell IC, Dauphin JF, Tallman JF, Murphy DL: changes in α and β receptor densities in rat brain as a result of treatment with monoamine oxidase inhibiting antidepressants . Neuropharmacology 1982;21:293-298.Crossref 12. Aulakh CS, Cohen RM, McLellan C, Murphy DL: Correlation of changes in α2-adrenoceptor number and locomotor responses to clonidine following clorgyline discontinuation . Br J Pharmacol 1983;80:10-12.Crossref 13. Pilc A, Vetulani J: Depression by chronic electroconvulsive treatment of clonidine hypothermia and 3H-clonidine binding to rat cortical membranes . Eur J Pharmacol 1982;80:109-113.Crossref 14. Vetulani J: Complex action of antidepressant treatment on central adrenergic system: Possible relevance to clinical effects . Pharmacopsychiatry 1984;17:16-21.Crossref 15. Smith CB, Moss SJ, Hollingsworth PJ: Lithium-induced changes in α2-adrenoreceptors in various rat brain regions . Fed Proc 1984;43:839. 16. Siever LJ, Uhde TW, Murphy DL: Possible subsensitization of α2-adrenergic receptors by chronic monoamine oxidase inhibitor treatment in psychiatric patients . Psychiatr Res 1982;6:293-297.Crossref 17. Charney DS, Heninger GR, Sternberg DE: α2-Adrenergic receptor sensitivity and the mechanism of action of antidepressant therapy: The effect of long-term amitriptyline treatment . Br J Psychiatry 1983;142:265-275.Crossref 18. Wood K, Coppen A: Prophylactic lithium treatment of patients with affective disorders is associated with decreased platelet 3H-dihydroergocryptine binding . J Affective Disord 1983;5:253-258.Crossref 19. Mitrius JC, Micuni M, Aora RC, Meltzer HY: Responsiveness of α2-adrenergic receptors is decreased in platelets from depressed patients . Neurosci Abstr 1983;9:990. 20. Daiguji M, Meltzer HY, Tong C, U'Prichard DC, Joung M, Kravitz H: α2-Adrenergic receptors in platelet membranes of depressed patients: No change in number or 3H-yohimbine affinity . Life Sci 1981;29:2059-2064.Crossref 21. Stahl SM, Lemoine PM, Ciaranello RD, Berger PA: Platelet α2-adrenergic receptor sensitivity in major depressive disorder . Psychiatr Res 1983;10:157-164.Crossref 22. Pimoule C, Briley MS, Gay C, Loo H, Sechter D, Zarifian E, Raisman R, Langer SZ: 3H-rauwolscine binding in platelets from depressed patients and healthy volunteers . Psychopharmacology 1983;79:308-312.Crossref 23. Hoffman BB, Lefkowitz RJ: Radioligand binding studies of adrenergic receptors: New insights into molecular and physiological regulation . Annu Rev Pharmacol Toxicol 1980;20:581-608.Crossref 24. Kahn DJ, Mitrius JC, U'Prichard DC: Alpha2-adrenergic receptors in neuroblastoma X glioma hybrid cells: Characterization with agonist and antagonist radioligand and relationship to adenylate cyclase . Mol Pharmacol 1982;21:17-26. 25. García-Sevilla JA, García-Vallejo P, Guimón J: Enhanced α2-adrenoceptor-mediated platelet aggregation in patients with major depressive disorder . Eur J Pharmacol 1983;94:359-360.Crossref 26. Kupfer DJ, Rush AJ: Recommendations for scientific reports on depression . Am J Psychiatry 1983;140:1327-1328. 27. American Psychiatric Association Committee on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders , ed 3. Washington, DC, 1980. 28. Hamilton M: A rating scale for depression . J Neurol Neurosurg Psychiatry 1960;23:56-62.Crossref 29. Amdisen A: Serum lithium determinations for clinical use . Scand J Clin Lab Invest 1967;20:104-108.Crossref 30. García-Sevilla JA, Hollingsworth PJ, Smith CB: Alpha2 adrenoreceptors on human platelets: Selective labelling by 3H-clonidine and 3H-yohimbine and competitive inhibition by antidepressant drugs . Eur J Pharmacol 1981;74:329-341.Crossref 31. Marquardt SW: An algorithm for least squares estimation of nonlinear parameters . J Soc Indust Appl Math 1963;11:431-437.Crossref 32. Lowry OH, Rosebrough NF, Farr AG, Randall RJ: Protein measurements with the Folin phenol reagent . J Biol Chem 1951;193:265-275. 33. Born GVR: Quantitative investigations into the aggregation of blood platelets . J Physiol 1962;162:67P-68P. 34. Hsu CY, Chung Y, Knapp DR, Haluska PV: The effects of α-adrenergic agents on human platelet aggregation . J Pharmacol Exp Ther 1979;208:366-370. 35. Grant JA, Scrutton MC: Interaction of selective α-adrenoceptor agonists and antagonists with human and rabbit blood platelets . Br J Pharmacol 1980;71:121-134. 36. Miller LH: Table of percentage point Kolmogoroff statistics . J Am Statist Assoc 1956;51:111-121.Crossref 37. Doyle MC, George AJ, Ravindran R: Platelet α2 receptor characteristics in depression and dementia, abstract 1986. Program and abstracts from the ninth international Congress of the International Union of Pharmacology, London, Aug 3, 1984. 38. Siever LJ, Kafka MS, Targum S, Lake CR: Platelet α-adrenergic binding and biochemical responsiveness in depressed patients and controls . Psychiatr Res 1984;11:287-302.Crossref 39. Clare KA, Scrutton MC, Thompson NT: Effects of α2-adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets . Br J Pharmacol 1984;82:467-476.Crossref 40. Rubinow DR, Post RM, Savard R, Gold PW: Cortisol hypersecretion and cognitive impairment in depression . Arch Gen Psychiatry 1984;41:279-283.Crossref 41. Newman M, Klein H, Bismaker B, Feinsod M, Belmaker RH: Lithium at therapeutic concentrations inhibits human brain noradrenaline-sensitive cyclic AMP accumulation . Brain Res 1983;278:380-381.Crossref 42. Belmaker RH: Adenylate cyclase and the search for new compounds with the clinical profile of lithium . Pharmacopsychiatry 1984;17:9-15.Crossref 43. Charney DS, Heninger GR, Sternberg DE, Hafstad KM, Giddings S, Landis DH: Adrenergic receptor sensitivity in depression: Effects of clonidine in depressed patients and healthy subjects . Arch Gen Psychiatry 1982;39:290-294.Crossref 44. Siever LJ, Uhde TW, Jimerson DC, Post RM, Lake CR, Murphy DL: Plasma cortisol responses to clonidine in depressed patients and controls . Arch Gen Psychiatry 1984;41:63-68.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Biochemical and Functional Evidence of Supersensitive Platelet α2-Adrenoceptors in Major Affective Disorder: Effect of Long-term Lithium Carbonate Treatment

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Publisher
American Medical Association
Copyright
Copyright © 1986 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1986.01800010053007
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Abstract

Abstract • The hypothesis that depressive illness is related to supersensitive α2-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 α2-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 affective disorder may be related to a dysfunction of the high-affinity state of the α2-adrenoceptor that recognizes agonists and mediates physiological effects. References 1. Charney DS, Menkes DB, Heninger GR: Receptor sensitivity and the mechanism of action of antidepressant treatment: Implications for the etiology and therapy of depression . Arch Gen Psychiatry 1981;38:1160-1180.Crossref 2. Cohen RM, Campbell IC, Cohen MR, Torda T, Pickar D, Siever LJ, Murphy DL: Presynaptic noradrenergic regulation during depression and antidepressant drug treatment . Psychiatr Res 1980;3:93-105.Crossref 3. Garcia-Sevilla JA, Zis AP, Hollingsworth PJ, Greden JF, Smith CB: Platelet α2-adrenergic receptors in major depressive disorder: Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment . Arch Gen Psychiatry 1981;38:1327-1333.Crossref 4. Smith CB, Garcia-Sevilla JA: α2-Adrenoreceptors in endogenous depression , in Langer SZ, Takanashi R, Segawa T, Briley M (eds): Advances in the Biosciences . New York, Pergamon Press, 1982, vol 40: New Vistas in Depression, pp 99-106. 5. Langer SZ: Presynaptic regulation of the release of catecholamines . Pharmacol Rev 1981;32:337-362. 6. Starke K: Presynaptic receptors . Annu Rev Pharmacol Toxicol 1981;21:7-30.Crossref 7. Bunney WE Jr, Davis JM: Norepinephrine in depressive reactions: A review . Arch Gen Psychiatry 1965;13:483-494.Crossref 8. Schildkraut JJ: The catecholamine hypothesis of affective disorders: A review of supporting evidence . Am J Psychiatry 1965;122:509-522. 9. Smith CB, García-Sevilla JA, Hollingsworth PJ: α2-Adrenoceptors in rat brain are decreased after long-term tricyclic antidepressant drug treatment . Brain Res 1981;210:413-418.Crossref 10. Pile A, Vetulani J: Attenuation by chronic imipramine treatment of 3H-clonidine binding to cortical membranes and of clonidine-induced hypothermia: The influence of central chemosympathectomy . Brain Res 1982;238:499-504.Crossref 11. Cohen RM, Campbell IC, Dauphin JF, Tallman JF, Murphy DL: changes in α and β receptor densities in rat brain as a result of treatment with monoamine oxidase inhibiting antidepressants . Neuropharmacology 1982;21:293-298.Crossref 12. Aulakh CS, Cohen RM, McLellan C, Murphy DL: Correlation of changes in α2-adrenoceptor number and locomotor responses to clonidine following clorgyline discontinuation . Br J Pharmacol 1983;80:10-12.Crossref 13. Pilc A, Vetulani J: Depression by chronic electroconvulsive treatment of clonidine hypothermia and 3H-clonidine binding to rat cortical membranes . Eur J Pharmacol 1982;80:109-113.Crossref 14. Vetulani J: Complex action of antidepressant treatment on central adrenergic system: Possible relevance to clinical effects . Pharmacopsychiatry 1984;17:16-21.Crossref 15. Smith CB, Moss SJ, Hollingsworth PJ: Lithium-induced changes in α2-adrenoreceptors in various rat brain regions . Fed Proc 1984;43:839. 16. Siever LJ, Uhde TW, Murphy DL: Possible subsensitization of α2-adrenergic receptors by chronic monoamine oxidase inhibitor treatment in psychiatric patients . Psychiatr Res 1982;6:293-297.Crossref 17. Charney DS, Heninger GR, Sternberg DE: α2-Adrenergic receptor sensitivity and the mechanism of action of antidepressant therapy: The effect of long-term amitriptyline treatment . Br J Psychiatry 1983;142:265-275.Crossref 18. Wood K, Coppen A: Prophylactic lithium treatment of patients with affective disorders is associated with decreased platelet 3H-dihydroergocryptine binding . J Affective Disord 1983;5:253-258.Crossref 19. Mitrius JC, Micuni M, Aora RC, Meltzer HY: Responsiveness of α2-adrenergic receptors is decreased in platelets from depressed patients . Neurosci Abstr 1983;9:990. 20. Daiguji M, Meltzer HY, Tong C, U'Prichard DC, Joung M, Kravitz H: α2-Adrenergic receptors in platelet membranes of depressed patients: No change in number or 3H-yohimbine affinity . Life Sci 1981;29:2059-2064.Crossref 21. Stahl SM, Lemoine PM, Ciaranello RD, Berger PA: Platelet α2-adrenergic receptor sensitivity in major depressive disorder . Psychiatr Res 1983;10:157-164.Crossref 22. Pimoule C, Briley MS, Gay C, Loo H, Sechter D, Zarifian E, Raisman R, Langer SZ: 3H-rauwolscine binding in platelets from depressed patients and healthy volunteers . Psychopharmacology 1983;79:308-312.Crossref 23. Hoffman BB, Lefkowitz RJ: Radioligand binding studies of adrenergic receptors: New insights into molecular and physiological regulation . Annu Rev Pharmacol Toxicol 1980;20:581-608.Crossref 24. Kahn DJ, Mitrius JC, U'Prichard DC: Alpha2-adrenergic receptors in neuroblastoma X glioma hybrid cells: Characterization with agonist and antagonist radioligand and relationship to adenylate cyclase . Mol Pharmacol 1982;21:17-26. 25. García-Sevilla JA, García-Vallejo P, Guimón J: Enhanced α2-adrenoceptor-mediated platelet aggregation in patients with major depressive disorder . Eur J Pharmacol 1983;94:359-360.Crossref 26. Kupfer DJ, Rush AJ: Recommendations for scientific reports on depression . Am J Psychiatry 1983;140:1327-1328. 27. American Psychiatric Association Committee on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders , ed 3. Washington, DC, 1980. 28. Hamilton M: A rating scale for depression . J Neurol Neurosurg Psychiatry 1960;23:56-62.Crossref 29. Amdisen A: Serum lithium determinations for clinical use . Scand J Clin Lab Invest 1967;20:104-108.Crossref 30. García-Sevilla JA, Hollingsworth PJ, Smith CB: Alpha2 adrenoreceptors on human platelets: Selective labelling by 3H-clonidine and 3H-yohimbine and competitive inhibition by antidepressant drugs . Eur J Pharmacol 1981;74:329-341.Crossref 31. Marquardt SW: An algorithm for least squares estimation of nonlinear parameters . J Soc Indust Appl Math 1963;11:431-437.Crossref 32. Lowry OH, Rosebrough NF, Farr AG, Randall RJ: Protein measurements with the Folin phenol reagent . J Biol Chem 1951;193:265-275. 33. Born GVR: Quantitative investigations into the aggregation of blood platelets . J Physiol 1962;162:67P-68P. 34. Hsu CY, Chung Y, Knapp DR, Haluska PV: The effects of α-adrenergic agents on human platelet aggregation . J Pharmacol Exp Ther 1979;208:366-370. 35. Grant JA, Scrutton MC: Interaction of selective α-adrenoceptor agonists and antagonists with human and rabbit blood platelets . Br J Pharmacol 1980;71:121-134. 36. Miller LH: Table of percentage point Kolmogoroff statistics . J Am Statist Assoc 1956;51:111-121.Crossref 37. Doyle MC, George AJ, Ravindran R: Platelet α2 receptor characteristics in depression and dementia, abstract 1986. Program and abstracts from the ninth international Congress of the International Union of Pharmacology, London, Aug 3, 1984. 38. Siever LJ, Kafka MS, Targum S, Lake CR: Platelet α-adrenergic binding and biochemical responsiveness in depressed patients and controls . Psychiatr Res 1984;11:287-302.Crossref 39. Clare KA, Scrutton MC, Thompson NT: Effects of α2-adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets . Br J Pharmacol 1984;82:467-476.Crossref 40. Rubinow DR, Post RM, Savard R, Gold PW: Cortisol hypersecretion and cognitive impairment in depression . Arch Gen Psychiatry 1984;41:279-283.Crossref 41. Newman M, Klein H, Bismaker B, Feinsod M, Belmaker RH: Lithium at therapeutic concentrations inhibits human brain noradrenaline-sensitive cyclic AMP accumulation . Brain Res 1983;278:380-381.Crossref 42. Belmaker RH: Adenylate cyclase and the search for new compounds with the clinical profile of lithium . Pharmacopsychiatry 1984;17:9-15.Crossref 43. Charney DS, Heninger GR, Sternberg DE, Hafstad KM, Giddings S, Landis DH: Adrenergic receptor sensitivity in depression: Effects of clonidine in depressed patients and healthy subjects . Arch Gen Psychiatry 1982;39:290-294.Crossref 44. Siever LJ, Uhde TW, Jimerson DC, Post RM, Lake CR, Murphy DL: Plasma cortisol responses to clonidine in depressed patients and controls . Arch Gen Psychiatry 1984;41:63-68.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Jan 1, 1986

References