Immunodetection and Quantitation of Imidazoline Receptor Proteins in Platelets of Patients With Major Depression and in Brains of Suicide Victims

Garcı́a-Sevilla, Jesús A.

doi:10.1001/archpsyc.1996.01830090049008

Cited by 89 publications

(80 citation statements)

References 50 publications

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“…It remains to be discovered what the function of this site is, but given the plethora of actions previously ascribed to clonidine (Buccafusco 1992), it should be of interest to psychiatry. Currently, we are attempting to determine whether this is the same I-site that was reported previously to be decreased in the hippocampus of depressed suicide victims (Piletz et al 2000b) and increased in the frontal cortex of depressed suicide victims (Garcia-Sevilla et al 1996).…”

Section: Discussionmentioning

confidence: 64%

Autoradiographic Comparison of [3H]-Clonidine Binding to Non-Adrenergic Sites and α2-Adrenergic Receptors in Human Brain

Piletz

Ordway

Zhu

et al. 2000

Neuropsychopharmacology

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Section: Discussionmentioning

confidence: 64%

Autoradiographic Comparison of [3H]-Clonidine Binding to Non-Adrenergic Sites and α2-Adrenergic Receptors in Human Brain

Piletz

Ordway

Zhu

et al. 2000

Neuropsychopharmacology

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“…This study was designed to evaluate the molecular alterations in the post-mortem brain of subjects with mood disorders who had committed suicide. Depression is the most important risk factor for suicide and, therefore, a common approach to study neurochemical alterations in mood disorders is the analysis of brain samples from suicide victims (García-Sevilla et al, 1996a). Indeed, no significant differences were found between GPCR expression in the brains of suicide victims with known (n ¼ 9) and unknown (n ¼ 3) history of depression.…”

Section: Discussionmentioning

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

121

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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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“…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: 91%

“…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. In another study of postmortem brain tissue, the binding ratio of p-[ 125 I]clonidine to IR-1 over α 2 -adrenoceptors was markedly increased in all orbital frontal cortical layers from depressed patients compared to the same layers from age/sex-matched control subjects with no history of depression .…”

Section: Introductionmentioning

confidence: 98%

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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Immunodetection and Quantitation of Imidazoline Receptor Proteins in Platelets of Patients With Major Depression and in Brains of Suicide Victims

Abstract: The results support a role for the newly discovered imidazoline receptors (mainly the 45-kd receptor expressed in the brain and platelets) in the pathogenesis of depression.

Cited by 89 publications

References 50 publications

Autoradiographic Comparison of [3H]-Clonidine Binding to Non-Adrenergic Sites and α2-Adrenergic Receptors in Human Brain

Autoradiographic Comparison of [3H]-Clonidine Binding to Non-Adrenergic Sites and α2-Adrenergic Receptors in Human Brain

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

Platelet imidazoline receptors as state marker of depressive symptomatology

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