Platelet 5-HT receptor binding during depressive illness and tricyclic antidepressant treatment

Cowen, Philip J.; Charig, Eileen M.; Fraser, Sheila; Elliott, J.M.

doi:10.1016/0165-0327(87)90072-3

Cited by 71 publications

(24 citation statements)

References 24 publications

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“…However, these findings have not always been confirmed (Cowen et al, 1987;Cheetham et al, 1988;McBride et al, 1994;Neuger et al, 1999). The number of platelet 5-HT 2A binding sites in manic subjects has also been reported to be the same as in controls (Velayudhan et al, 1999).…”

Section: Discussionmentioning

confidence: 60%

Altered 5-HT-Induced Calcium Response in the Presence of Staurosporine in Blood Platelets from Bipolar Disorder Patients

Suzuki

Kusumi

Akimoto

et al. 2003

Neuropsychopharmacol

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We have reported that the platelet intracellular calcium (Ca) mobilization after stimulation by serotonin (5-HT) is specifically enhanced in bipolar disorder among various psychiatric disorders, compared with that in normal control. To explore the mechanisms of enhanced Ca response to 5-HT in the platelets, we first examined the relation between the 5HT-elicited Ca mobilization and 5-HT 2A receptor density using the platelets from 13 normal subjects. From this study, we found no significant correlation between two measures. Then, we investigated the effects of staurosporine, a protein kinase C (PKC) inhibitor, on Ca response to 5-HT in platelets from patients with major depressive disorder (unipolar), bipolar disorder, and normal controls. While 5-HT-induced Ca mobilization, in the presence of 100 nM staurosporine, was significantly attenuated in normal controls and patients with major depressive disorder, the inhibitory effect of staurosporine was not observed in bipolar disorder. These results suggest that the failure in inhibiting the platelet intracellular Ca response to 5-HT in bipolar disorder may be related to increased activity of PKC rather than increased 5-HT 2A receptor number. Moreover, the trend of the Ca response towards staurosporine may become a specific biological marker for unipolar-bipolar dichotomy.

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Section: Discussionmentioning

confidence: 60%

Altered 5-HT-Induced Calcium Response in the Presence of Staurosporine in Blood Platelets from Bipolar Disorder Patients

Suzuki

Kusumi

Akimoto

et al. 2003

Neuropsychopharmacol

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“…It seems evident that interfering factors such as the protein content must be kept constant (e.g., by pre-adjusting protein concentrations in membrane suspensions of different individuals with a rapid protein assay) within and between studies. Variations of these factors may account for discrepant results in different studies comparing depressed with non-depressed patients; thus, Cowen et al (1987) failed to detect any differences between depressed and non-depressed patients in platelet 5-HT 2 receptor binding when using intact platelets for binding studies. Analysis of 5-HT 2 receptor binding between subjects and within subjects over time indicated that there was considerable variation of density and affinity.…”

Section: [3h]lsd Bindingmentioning

confidence: 68%

“…In general, two main ligands have been used in order to study the platelet 5-HT 2 receptor in humans as well as in other species: ketanserin (Leysen et al, 1983(Leysen et al, , 1991Biegon et al, 1987Biegon et al, , 1990Biegon et al, , 1992 and lysergic acid diethylamide (LSD; Geaney et al, 1984;Cowen et al, 1987;McBride et al, 1987;Arora and Meltzer, 1989;Best etal., 1989;Elliott and Kent, 1989;Pandey etal., 1990;Twist etal., 1990). Since the choice of ligand and other aspects of the assay methods may contribute to discrepant results in 5-HT 2 receptor binding characteristics on depressed patient's platelet membranes observed by different authors (Meltzer and Arora, 1991), a critical investigation and characterization of 5-HT 2 receptor binding assays seems to be necessary.…”

Section: Introductionmentioning

confidence: 99%

Human platelet 5-HT2 receptor binding sites re-evaluated: A criticism of recurrent techniques

Steckler

Rüggeberg-Schmidt

Müller‐Oerlinghausen

1993

J. Neural Transmission

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The human platelet 5-HT2 receptor may resemble a peripheral model of central 5-HT2 binding sites and has been linked to changes in 5-HT2 receptor function in depression. Therefore, evaluation of the human platelet 5-HT2 binding characteristics is important. Comparing [3H]ketanserin and [3H]LSD as ligands clearly indicated [3H]LSD as ligand of choice for binding studies dealing with the human platelet 5-HT2 receptor. [3H]LSD binding was specific, saturable, and depended upon incubation time, protein concentration and previous handling of tissue, i.e., use of fresh or frozen tissue. In contrast, studies with [3H]ketanserin were unsatisfactory. Although mean receptor densities and affinities have been relatively constant between individuals and over time in healthy subjects with [3H]LSD, examination of the individual data showed considerable variations within single subjects. Thus, KD ranged between 0.50 and 0.68 nM, and Bmax was in the range of 64.9 to 97.1 fmol/mg protein in healthy individual subjects. Therefore, we recommend [3H]LSD as ligand of choice to study platelet 5-HT2 receptor binding in humans. Furthermore, repeated measurement of individual data over time should be interpreted cautiously, especially when data from depressed patients are under examination.

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“…The density of 5-HT 2A receptors was found to be decreased after antidepressant treatment in binding studies in rat brain (Peroutka and Snyder, 1980;Kellar et al, 1981;Goodnough and Baker, 1994), in PET studies in depressed subjects (Meyer et al, 2001;Yatham et al, 1999) and in some (Biegon et al, 1987;Stahl et al, 1993), but not all (Cowen et al, 1987;Bakish et al, 1997), platelet binding studies in major depression. However, these methods are not comparable to functional ones, since they measure different receptor parameters.…”

Section: Discussionmentioning

confidence: 94%

Decrease of the platelet 5‐HT_2A receptor function by long‐term imipramine treatment in endogenous depression

Gómez‐Gil¹,

Gastó²,

Carretero

et al. 2004

Human Psychopharmacology

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The results showed a decrease in a platelet functional response mediated by 5-HT2A receptors following effective imipramine treatment, suggesting that desensitization or down-regulation of the 5-HT2A receptor function could be linked to the therapeutic effect of some antidepressants. The data also support the use of platelet aggregometry as a surrogate measurement of antidepressant action, particularly in intra-subject designs.

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Platelet 5-HT receptor binding during depressive illness and tricyclic antidepressant treatment

Cited by 71 publications

References 24 publications

Altered 5-HT-Induced Calcium Response in the Presence of Staurosporine in Blood Platelets from Bipolar Disorder Patients

Altered 5-HT-Induced Calcium Response in the Presence of Staurosporine in Blood Platelets from Bipolar Disorder Patients

Human platelet 5-HT2 receptor binding sites re-evaluated: A criticism of recurrent techniques

Decrease of the platelet 5‐HT_2A receptor function by long‐term imipramine treatment in endogenous depression

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Platelet 5-HT receptor binding during depressive illness and tricyclic antidepressant treatment

Cited by 71 publications

References 24 publications

Altered 5-HT-Induced Calcium Response in the Presence of Staurosporine in Blood Platelets from Bipolar Disorder Patients

Altered 5-HT-Induced Calcium Response in the Presence of Staurosporine in Blood Platelets from Bipolar Disorder Patients

Human platelet 5-HT2 receptor binding sites re-evaluated: A criticism of recurrent techniques

Decrease of the platelet 5‐HT2A receptor function by long‐term imipramine treatment in endogenous depression

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Decrease of the platelet 5‐HT_2A receptor function by long‐term imipramine treatment in endogenous depression