Platelet I1-imidazoline binding sites are elevated in depression but not generalized anxiety disorder

Piletz, John E.; Halaris, Angelos; Nelson, Jill; Qu, Yinsheng; Bari, Mohammed Abdul

doi:10.1016/0022-3956(96)00005-2

Cited by 43 publications

(32 citation statements)

References 53 publications

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“…Previous studies have shown that IR-1 are increased in frontal cortex and platelets of depressed patients (Garcia-Sevilla et al, 1996;Piletz et al, 2003a;Piletz, Halaris, Nelson, Qu, & Bari, 1996a;Piletz, Halaris, Saran, & Marler, 1991;Piletz, Halaris, Chikkala, & Qu, 1996b;Piletz, Schubert, & Halaris, 1986), and this up-regulation is normalized (down-regulated) after antidepressant drug treatments (Garcia-Sevilla et al, 1996;Piletz et al, 1991;Piletz et al, 1996b;Zhu et al, 1999;Zhu, Halaris, & Piletz, 1997). In two western blotting studies, the immunoreactivity of IRAS in 33 kD and 45 kD bands (peptides of IRAS (Zhu, Hayes, Chen, Baldwin, & Piletz, 2003a) was increased in platelets and prefrontal cortical membranes (Garcia-Sevilla et al, 1996) but decreased in hippocampal homogenates (Piletz et al, 2000b) from depressed patients relative to matched controls.…”

Section: Introductionmentioning

confidence: 93%

Platelet imidazoline receptors as state marker of depressive symptomatology

Piletz

Baker

Halaris

2008

Journal of Psychiatric Research

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Objective-Previous studies have shown that imidazoline receptors (IR-1) are increased in platelets and frontal cortex of depressed patients, and this up-regulation is normalized (down-regulated) after antidepressant drug treatments. It has been hypothesized that IR-1 up-regulation during the depressive episode may be a state marker for depressive symptomatology. The goal of the present study was to address the state versus trait question.Method-Twelve healthy subjects (6 males and 6 females) met stringent inclusion and exclusion criteria for physical and mental health. They received desipramine for six weeks in order to simulate the length of time and dosing used previously to obtain an IR-1 down-regulation and a therapeutic response in depressed patients. Outcome and safety measures included clinical, psychological, and cardiovascular assessments obtained throughout the study. Plasma concentrations of desipramine were measured throughout the six weeks of treatment and again after 2 weeks following tapered discontinuation of desipramine. Platelet receptors were assessed by Western blotting and radioligand binding assays.Results-Healthy subjects taking desipramine experienced mild dysphoric effects but there were no adverse events. The binding of 8 nM p-[ 125 I] clonidine to IR-1 and α 2 -adrenoceptors in healthy subjects did not change during desipramine treatment. The immunodensity of the 33 kD band associated with IR-1 gradually increased to a maximum, by week-6, of 26% higher than baseline (p < 0.01 compared to baseline). Two weeks after desipramine discontinuation, there was a decline in α 2 -adrenoceptor binding and 33 kD band's immunodensity (p = 0.04).Conclusions-The findings support the hypothesis that platelet IR-1 binding sites are a marker of mood state rather than of antidepressant-induced pharmacological regulation. By comparison, platelet α 2 -adrenoceptors appear to be regulated by desipramine as a pharmacological effect independent of mood state.

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Section: Introductionmentioning

confidence: 93%

Platelet imidazoline receptors as state marker of depressive symptomatology

Piletz

Baker

Halaris

2008

Journal of Psychiatric Research

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“…In this context, it is well accepted that antidepressant treatments induce down-regulation and desensitization of a2-adrenoceptors in the platelets of depressed patients (a2A subtype) (Garcia-Sevi!la et a Piletz and Halaris, 1988;Pandey et a!., 1989;Karege et al, 1992;Piletz et al, 1996) and in the rat CNS Nomura et al, 1987;Giralt and GarcIa-Sevilla, 1989;Menargues et a!., 1990;Heal t a!., 1991;Mongeau et al, 1994). Therefore, a possible down-regulation of brain a2-adrenoceptors by chronic antidepressant treatment could be expected in the suicide group (De Paermentier et a!., 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies performed in platelets of depressed patients have shown an increased a2-adrenoceptor density Doyle et al, 1985;Piletz and Halaris, 1988;Piletz et al, 1990Piletz et al, , 1991; for review, see Piletz and Halaris, 1994) associated with an enhanced receptor sensitivity (GarcIaSevilla et al, 1986(GarcIaSevilla et al, , 1990Karege et al, 1996). In this context, it has been also demonstrated that a variety of antidepressant drug treatments, as well as electroconvulsive therapy, decrease and/or reverse the enhanced density and sensitivity of platelet a2-adrenoceptors in depressed patients Piletz and Halaris, 1988;Pandey et al, 1989;Karege et al, 1992;Piletz et al, 1996). In the rat CNS, several antidepressant treatments, when given chronically, reduce the density and activity of a2-adrenoceptors Nomura et al, 1987;Giralt and GarcIa-Sevilla, 1989;Menargues et al, 1990;Heal et al, 1991;Mongeau et al, 1994).…”

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confidence: 99%

Selective Increase of α_2A‐Adrenoceptor Agonist Binding Sites in Brains of Depressed Suicide Victims

Callado

Meana

Grijalba

et al. 1998

Journal of Neurochemistry

132

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“…Thus, increases of a 2 -adrenoceptor and Gi protein density/activity, and decreases of adenylyl cyclase density/activity would be involved with reductions in cytosolic levels of cAMP. Moreover, antidepressant drug treatment has been shown to decrease the levels of a 2A -adrenoceptors and Gi proteins, further implicating these receptors in the pathophysiology, and thus, in the therapy of suicide, and depression (De Paermentier et al, 1997;García-Sevilla et al, 1986;Piletz et al, 1996).…”

Section: Alterations In a 2a -Ar Expression In The Brains Of Suicidesmentioning

confidence: 99%

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

Escribá

Ozaita

Garcı́a-Sevilla

2004

Neuropsychopharmacol

124

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The development of new therapies for the treatment of psychiatric disorders requires an in-depth knowledge of the molecular bases underlying these pathologies, which remain largely unknown. Alterations in adrenoceptors, serotonin receptors, and other G proteincoupled receptors (GPCRs) have been associated with suicide and depression. However, to date, there is little information about mRNA expression of the GPCRs in the frontal cortex of suicide victims. Our goal was to study the expression in the brain of these receptors. For this purpose, we measured mRNA levels by RT-PCR. We found that the expressions of a 2A -adrenoceptors, 5-HT 1A , 5-HT 2A serotonin receptors, and m-opioid receptors were elevated in the post-mortem brains of these suicide victims with respect to matched controls. Moreover, in the case of a 2A -adrenoceptors (the only for which these data were available), a significant correlation was observed between the level of mRNA and protein quantified in the brain of the same subjects, indicating that protein synthesis of this receptor was not influenced by post-translational regulatory mechanisms. In addition, the degree of adrenoceptor and 5-HT receptor expressions appeared to be correlated in the brains of suicide victims and control subjects. Alterations in the expression of adrenoceptors, serotonin, and opioid receptors indicate that these signaling proteins might be related to the etiopathology of suicidal and depressive behaviors. Alternatively, such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations. The results also suggest that these receptors could share common regulatory mechanisms.

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Platelet I1-imidazoline binding sites are elevated in depression but not generalized anxiety disorder

Cited by 43 publications

References 53 publications

Platelet imidazoline receptors as state marker of depressive symptomatology

Platelet imidazoline receptors as state marker of depressive symptomatology

Selective Increase of α_2A‐Adrenoceptor Agonist Binding Sites in Brains of Depressed Suicide Victims

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

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Platelet I1-imidazoline binding sites are elevated in depression but not generalized anxiety disorder

Cited by 43 publications

References 53 publications

Platelet imidazoline receptors as state marker of depressive symptomatology

Platelet imidazoline receptors as state marker of depressive symptomatology

Selective Increase of α2A‐Adrenoceptor Agonist Binding Sites in Brains of Depressed Suicide Victims

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

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Selective Increase of α_2A‐Adrenoceptor Agonist Binding Sites in Brains of Depressed Suicide Victims