Biomedical subjects

J Guimón

Publications and source records attributed to J Guimón.

At least 19 recordsLinked to original sources

PubMed2002

Neurotransmitter receptor-mediated activation of G-proteins in brains of suicide victims with mood disorders: selective supersensitivity of alpha(2A)-adrenoceptors.

Abnormalities in the density of neuroreceptors that regulate norepinephrine and serotonin release have been repeatedly reported in brains of suicide victims with mood disorders. Recently, the modulation of the [(35)S]GTPgammaS binding to G-proteins has been introduced as a suitable measure of receptor activity in postmortem human brain. The present study sought to evaluate the function of several G-protein coupled receptors in postmortem brain of suicide victims with mood disorders. Concentration-response curves of the [(35)S]GTPgammaS binding stimulation by selective agonists of alpha(2)-adrenoceptors, 5-HT(1A) serotonin, mu-opioid, GABA(B), and cholinergic muscarinic receptors were performed in frontal cortical membranes from 28 suicide victims with major depression or bipolar disorder and 28 subjects who were matched for gender, age and postmortem delay. The receptor-independent [(35)S]GTPgammaS binding stimulation by mastoparan and the G-protein density were also examined. The alpha(2A)-adrenoceptor-mediated stimulation of [(35)S]GTPgammaS binding with the agonist UK14304 displayed a 4.6-fold greater sensitivity in suicide victims than in controls, without changes in the maximal stimulation. No significant differences were found in parameters of 5-HT(1A) serotonin receptor and other receptor-mediated [(35)S]GTPgammaS binding stimulations. The receptor-independent activation of G-proteins was similar in both groups. Immunoreactive densities of G(alphai1/2)-, G(alphai3)-, G(alphao)-, and G(alphas)-proteins did not differ between suicide victims and controls. In conclusion, alpha(2A)-adrenoceptor sensitivity is increased in the frontal cortex of suicide victims with mood disorders. This receptor supersensitivity is not related to an increased amount or enhanced intrinsic activity of G-proteins. The new finding provides functional support to the involvement of alpha(2)-adrenoceptors in the pathogenesis of mood disorders.

Adult↗

PubMed2001

Acute and chronic effects of morphine and naloxone on the phosphorylation of neurofilament-H proteins in the rat brain.

Increased amounts of phosphorylated neurofilaments (pNF-H and pNF-M) are found in postmortem brains of opioid addicts. Because of the potential relevance of aberrant pNF in opioid addiction (alterations of neuronal cytoskeleton and associated functions), the effects of opiate drugs on pNF-H were investigated in rat brain. Acute morphine (30 mg/kg, 2 h) induced a marked increase in the immunodensity of pNF-H in the cerebral cortex (93%). Chronic morphine (10-100 mg/kg for 5 days) followed by opiate withdrawal resulted in a time-dependent decline in pNF-H (induction of tolerance). Thus, 2 h after the last dose of morphine, the abundance of pNF-H was still increased (27%), which was followed (6-24 h) by down-regulation of pNF-H (5% increase at 6 h; 5% decrease at 12 h, and 29% decrease at 24 h). The acute (10 mg/kg for 2 h) and chronic (2 x 10 mg/kg for 14 days) treatments with naloxone, an opioid receptor antagonist, did not alter pNF-H in the cerebral cortex, suggesting that the opioid receptors (probably the mu-type) modulating the phosphorylation state of NF-H are not tonically activated by endogenous opioids. The results indicate that morphine addiction is associated with an aberrant hyperphophorylation of NF-H in the rat brain.

Animals↗

PubMed2001

Cyclic AMP-mediated signaling components are upregulated in the prefrontal cortex of depressed suicide victims.

The components of cyclic AMP signaling cascade (catalytic (Calpha) subunit of cyclic AMP-dependent protein kinase (PKA) and cyclic AMP response element binding protein (CREB)) were quantitated by Western blotting in the prefrontal cortex of depressed suicide victims (n=23) and their matched controls (n=14). There was a significant increase in the levels of CREB, both in total (tCREB; 121+/-8% (mean+/-S.E.M.), P<0.02) and phosphorylated (pCREB; 128+/-9%, P<0.01) forms, but not in PKA Calpha levels (109+/-9%, ns), in brains of depressed suicides compared to those in control subjects. The increases in CREB were specifically observed in antidepressant drug-free subjects (tCREB: 137+/-11%, P<0.01; pCREB: 136+/-12%, P<0.02; n=9), but not in the antidepressant-treated subjects (tCREB: 108+/-18%, ns; pCREB: 111+/-17%, ns; n=8). There were significant correlations between the levels of PKA and those of tCREB and pCREB in the prefrontal cortex of depressed suicides. These results indicate that the components of cyclic AMP signaling are upregulated in a coordinated manner in brains of depressed suicides and that this alteration is not related to antidepressant treatment.

Adult↗

PubMed2001

Relationships between beta- and alpha2-adrenoceptors and G coupling proteins in the human brain: effects of age and suicide.

Interactions between brain alpha2- and beta-adrenoceptors are of interest in physiological (aging) and pathological (major depression) processes involving both receptors. In this study, total beta-adrenoceptors and beta1/2-subtypes were quantitated in postmortem human brains to investigate their relationships with alpha2A-adrenoceptors and specific G proteins during the process of aging and in brains of suicide victims. Analysis of [3H]CGP12177 binding, in the presence of CGP20712A (beta1-antagonist), indicated that the predominant beta-adrenoceptor in the frontal cortex is the beta1-subtype (65-75%). The density of total beta- (r=-0.60, n=44) or beta1-adrenoceptors (r=-0.78, n=22), but not the beta2-subtype, declined with aging (3-80 years). The density of total beta- or beta1-adrenoceptors, but not the beta2-subtype, correlated with the number of alpha2-adrenoceptors quantitated in the same brains with the agonist [3H]UK14304 (r=0.71-0.81) or the antagonist [3H]RX821002 (r=0.61-0.66). Interestingly, the ratios alpha2/beta- or alpha2/beta1-adrenoceptors did not correlate with the age of the subject at death, indicating that the proportion of alpha2/beta-adrenoceptors in brain remains rather constant during the process of aging. The density of beta-adrenoceptors correlated with the immunodensity of G(alpha)s (r=0.55) and Gbeta (r=0.61) proteins, and that of alpha2-adrenoceptors with those of G(alpha)i1/2 (r=0.88) and Gbeta (r=0.65). In brains of suicides, compared to controls, the ratio between alpha2- and beta- or beta1-adrenoceptors (alpha2-full agonist sites/beta-sites) was greater (1.3- to 2.0-fold; P<0.05). The results demonstrate a close interdependence between brain alpha2- and beta-adrenoceptors during aging, and in brains of suicides. The quantitation of the alpha2A/beta-adrenoceptor ratio could represent a relevant neurochemical index in the study of brain pathologies in which both receptors are involved.

Adolescent↗

PubMed2000

Regulation of nonphosphorylated and phosphorylated forms of neurofilament proteins in the prefrontal cortex of human opioid addicts.

The neurofilament (NF) proteins (NF-H, NF-M, and NF-L for high, medium, and low molecular weights) play a crucial role in the organization of neuronal shape and function. In a preliminary study, the abundance of total NF-L was shown to be decreased in brains of opioid addicts. Because of the potential relevance of NF abnormalities in opioid addiction, we quantitated nonphosphorylated and phosphorylated NF in postmortem brains from 12 well-defined opioid abusers who had died of an opiate overdose (heroin or methadone). Levels of NF were assessed by immunoblotting techniques using phospho-independent and phospho-dependent antibodies, and the relative (% changes in immunoreactivity) and absolute (changes in ng NF/microg total protein) amounts of NF were calculated. Decreased levels of nonphosphorylated NF-H (42-32%), NF-M (14-9%) and NF-L (30-29%) were found in the prefrontal cortex of opioid addicts compared with sex, age, and postmortem delay-matched controls. In contrast, increased levels of phosphorylated NF-H (58-41%) and NF-M (56-28%) were found in the same brains of opioid addicts. The ratio of phosphorylated to nonphosphorylated NF-H in opioid addicts (3.4) was greater than that in control subjects (1.6). In the same brains of opioid addicts, the levels of protein phosphatase of the type 2A were found unchanged, which indicated that the hyperphosphorylation of NF-H is not the result of a reduced dephosphorylation process. The immunodensities of GFAP (the specific glial cytoskeletol protein), alpha-internexin (a neuronal filament related to NF-L) and synaptophysin (a synapse-specific protein) were found unchanged, suggesting a lack of gross changes in glial reaction, other intermediate filaments of the neuronal cytoskeletol, and synaptic density in the prefrontal cortex of opioid addicts. These marked reductions in total NF proteins and the aberrant hyperphosphorylation of NF-H in brains of opioid addicts may play a significant role in the cellular mechanisms of opioid addiction.

Adult↗

PubMed2000

Wavelet analysis of dynamic PET data: application to the parametric imaging of benzodiazepine receptor concentration.

Receptor density and ligand affinity can be assessed using positron emission tomography (PET). Biological parameters (B(max)('), k(1), k(2), k(on)/V(R), k(off)) are estimated using a compartmental model and a multi-injection protocol. Parametric imaging of the ligand-receptor model has been shown to be of special interest to study certain brain disorders. However, the low signal-to-noise ratio in kinetic curves at the pixel level hampers an adequate estimation of model parameters during the optimization procedure. For this reason, mapping requires a spatial filter, resulting in a loss of resolution. Filtering the kinetic curves in the frequency domain using the Fourier transform is not appropriate, because of difficulties in choosing a correct and efficient cutoff frequency. A wavelet-based filter is more appropriate to such tracer kinetics. The purpose of this study is to build up parametric images at the pixel level while conserving the original spatial resolution, using wavelet-based filtering. Data from [(11)C]flumazenil studies, mapping the benzodiazepine receptor density, were used. An invertible discrete wavelet transform was used to calculate the time-frequency signals of the time-concentration PET curves on a pixel-by-pixel basis. Kinetic curves observed from large regions of interest in high and low receptor-density regions were used to calibrate the threshold of wavelet coefficients. The shrunken wavelet coefficients were then transformed back to the original domain in order to obtain the filtered PET signal. Maps of all binding parameters were obtained at the pixel level with acceptable coefficients of variation of less than 30% for the B(max)(') parameter in most of the gray matter. A strong correlation between model parameter estimates using the usual regions of interest and parametric imaging was observed for all model parameters (r = 0.949 for the parameter B(max)(')). We conclude that wavelet-based filters are useful for building binding parameter maps without loss of the original spatial resolution of the PET scanner. The use of the wavelet-based filtering method can be extended far beyond the multi-injection protocol. It is likely to be also effective for other dynamic PET studies.

Brain↗

PubMed2000

mu-opioid receptor and alpha2-adrenoceptor agonist stimulation of [35S]GTPgammaS binding to G-proteins in postmortem brains of opioid addicts.

Repeated opioid administration has been associated in human brain with unaltered density of mu-opioid receptors (agonist radioligand binding sites and immunodetected receptor protein). These receptors are coupled to Gi/Go-proteins, which are increased in brain of heroin addicts. To assess the activity of G-proteins and their coupling to receptors after chronic opioid abuse, [35S]GTPgammaS binding was quantified in postmortem prefrontal cortices of 15 opioid-dependent subjects and 15 matched controls. The stimulation of [35S]GTPgammaS binding by the mu-opioid receptor agonist DAMGO or the alpha2-adrenoceptor agonist UK14304 was used as a functional measure of the status of the receptor-G-protein coupling. [35S]GTPgammaS binding basal values were similar in opioid addicts (819+/-83 fmol mg-1 of protein) and controls (918+/-106 fmol mg(-1) of protein). In opioid addicts, [35S]GTPgammaS binding stimulation by DAMGO showed a maximal effect (62+/-8%) and a potency (EC50 = 1.09+/-0.26 microM) that did not differ from the maximal effect (60+/-12%) and potency (EC50 = 2.01+/-0.58 microM) in controls. In opioid addicts, [35S]GTPgammaS binding stimulation by UK14304 was not different in maximal effect (28+/-3%) from controls (32+/-8%), but the potency of the agonist was decreased (EC50 = 4.36+/-1.81 microM) when compared with controls (EC50 = 0.41+/-0.15 microM). The results provide a direct evidence of an apparent normal functional activity of brain mu-opioid receptors (Gi/Go-protein coupling) during the opioid dependence process in humans. The data also demonstrate a functional uncoupling of alpha2-adrenoceptors from G-proteins, which indicates a heterologous desensitization of these receptors. This finding could represent an adaptive mechanism against the decreased noradrenergic activity induced by the chronic presence of opioid drugs.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1999

Imidazoline receptors and human brain disorders.

Major depression, opioid addiction, neurodegenerative diseases, and glial tumors are associated with disturbances of imidazoline receptors (IR) in the human brain. In depression, the level of a 45-kD IR protein (putative I1-IR) is increased in the brain of suicide victims (51%) and in platelets of depressed patients (40%). The density of platelet I1-IR ([125I]-p-iodoclonidine binding) is also increased in depression (135%). The 29/30-kD IR protein (putative I2B-IR) is downregulated (19%) in suicide victims in parallel with a reduction (40%) in the density of I2B-IR ([3H]idazoxan binding). Antidepressant drugs induce downregulation of 45-kD IR protein and I1-sites in platelets of depressed patients and upregulation of I2-sites in rat brain. The densities of I2B-IR and the related 29/30-kD IR protein are decreased (39% and 28%) in the brain of heroin addicts. The density of I2B-IR is increased in Alzheimer's disease (63%) and decreased in Huntington's disease (56%). Brain I2B-IR is not altered in Parkinson's disease. The level of I2-IR in glial tumors is increased (two-fivefold) in parallel with the abundance of the related 29/30-kD IR protein (39%), whereas the level of 45-kD IR protein is decreased (39%). The possible functional relevance of these findings in the context of the pathogenesis of these disorders remains to be elucidated.

Alcoholism↗

PubMed1999

[Professional practice and theoretical orientation of women and men psychiatrists].

RESEARCH QUESTIONS: Differences between male and female psychiatrists in their careers, professional and clinical activities, and clinical orientations, in general and in contrasted settings for the practice of psychiatry. METHODS: Survey by mailed questionnaire to psychiatrists working in private practice or in institutions. RESULTS: Male and female psychiatrists share some similar characteristics (age, many interests, etc.). However, female psychiatrists differ from male psychiatrists in numerous respects: more frequently engaged in private practice, shorter work-weeks, less diversification of clinical activities, more frequent reference to a psychological model. In women occupying hierarchic positions, these differences disappear, whilst they are maintained in private practice for those using the psychological model. The differences can be interpreted in part in terms of gender-specific socialization, but their origin could mainly arise from the existence of different systems of gender-based constraints in the management of professional and personal, or family, spheres. CONCLUSIONS: Adjusting the training period and working conditions in institutions could facilitate career diversification for both male and female psychiatrists.

Adult↗

PubMed1999

Objectives for the undergraduate teaching of psychiatry: survey of doctors and students.

OBJECTIVES: The principal aim was to assess the psychiatric topics that doctors and students considered most important for undergraduate teaching. Differences between doctors and students, men and women, physicians/students with or without an interest in psychiatry were examined. DESIGN: A mailed questionnaire was used concerning the knowledge and skills of psychological/psychiatric medi- cine considered to be needed in medical practice. SETTING: The Medical School of the University of Geneva. SUBJECTS: Doctors and undergraduate medical students in their last 2 years of medical training. RESULTS: Both doctors and students agreed on most topics, even though the students tended to give all items a higher rating. Both groups agreed on the importance of the following main topics: the doctor-patient relationship, identification and management of the principal psychiatric disorders and their associated risks and problems of a psychosocial nature. Those doctors showing an interest in psychiatry tended to accentuate the importance attached to interpersonal skills. The male and female doctors and students expressed very similar opinions. The female doctors, however, tended to attach greater importance to relational-emotional aspects and to disorders affecting children and adolescents than did their male colleagues, which is probably a reflection of the specific role that women still play within our society. When asked to assess the current teaching they received in medical school, the students considered that certain important aspects of psychiatry were insufficiently taught. CONCLUSION: These results confirm the importance of teaching psychiatry with an emphasis on problems encountered in general practice.

Attitude of Health Personnel↗

PubMed1999

Up-regulation of immunolabeled alpha2A-adrenoceptors, Gi coupling proteins, and regulatory receptor kinases in the prefrontal cortex of depressed suicides.

Suicide and depression are associated with an increased density of alpha2-adrenoceptors (radioligand receptor binding) in specific regions of the human brain. The function of these inhibitory receptors involves various regulatory proteins (Gi coupling proteins and G protein-coupled receptor kinases, GRKs), which work in concert with the receptors. In this study we quantitated in parallel the levels of immunolabeled alpha2A-adrenoceptors and associated regulatory proteins in brains of suicide and depressed suicide victims. Specimens of the prefrontal cortex (Brodmann area 9) were collected from 51 suicide victims and 31 control subjects. Levels of alpha2A-adrenoceptors, Galphai1/2 proteins, and GRK 2/3 were assessed by immunoblotting techniques by using specific polyclonal antisera and the immunoreactive proteins were quantitated by densitometry. Increased levels of alpha2A-adrenoceptors (31-40%), Galphai1/2 proteins (42-63%), and membrane-associated GRK 2/3 (24-32%) were found in the prefrontal cortex of suicide victims and antidepressant-free depressed suicide victims. There were significant correlations between the levels of GRK 2/3 (dependent variable) and those of alpha2A-adrenoceptors and Galphai1/2 proteins (independent variables) in the same brain samples of suicide victims (r = 0.56, p = 0.008) and depressed suicide victims (r = 0.54, p = 0.041). Antemortem antidepressant treatment was associated with a significant reduction in the levels of Galphai1/2 proteins (32%), but with modest decreases in the levels of alpha2A-adrenoceptors (6%) and GRK 2/3 (18%) in brains of depressed suicide victims. The increased levels in concert of alpha2A-adrenoceptors, Galphai1/2 proteins, and GRK 2/3 in brains of depressed suicide victims support the existence of supersensitive alpha2A-adrenoceptors in subjects with major depression.

Adult↗

PubMed1998

Imidazoline receptor proteins in brains of patients with Alzheimer's disease.

Imidazoline receptors (29/30- and 45-kDa proteins) were quantitated in postmortem brains of patients with Alzheimer's disease (AD) by using immunoblotting techniques and a specific antiserum. Increased levels of the 29/30-kDa protein (30%), 45-kDa protein (36%) and glial fibrillary acidic protein (88%) were found in the frontal cortex of AD patients. These findings are in line with the reported higher density of imidazoline receptors labelled by [3H]idazoxan in AD brains, suggesting that these imidazoline receptor proteins are related to the I2-imidazoline receptor located in mitochondria of glial (astrocyte) cells.

Aged↗

PubMed1998

Density of imidazoline receptors in platelets of euthymic patients with bipolar affective disorder and in brains of lithium-treated rats.

BACKGROUND: Platelet imidazoline receptors have been shown to be up-regulated in patients with unipolar major depression. This study examines the status of imidazoline receptor proteins in platelets of euthymic bipolar patients and in brains of lithium-treated rats. METHODS: Platelets were collected from 12 bipolar patients (lithium-treated or drug-free) and brains from chronic lithium-treated rats. Imidazoline receptors were quantitated by immunoblotting, using a specific antiserum, and/or radioligand binding. RESULTS: No changes in platelet imidazoline receptors (35-kDa and 45-kDa proteins) were found. Lithium treatment did not alter brain imidazoline receptors (29/30-kDa, 45-kDa, and 66-kDa proteins or density/affinity of [3H]-idazoxan binding sites). CONCLUSIONS: Imidazoline receptor proteins are not altered in platelets of euthymic patients with bipolar affective disorder.

Adult↗

PubMed1997

Density of guanine nucleotide-binding proteins in platelets of patients with major depression: increased abundance of the G alpha i2 subunit and down-regulation by antidepressant drug treatment.

The aim of this study was to quantitate the density of guanine nucleotide-binding (G) protein subunits (inhibitory G alpha i, stimulatory G alpha s, G alpha q/11, and G beta) in platelets of unipolar depressed patients to assess the status of these signal transduction proteins in depression and the effects of antidepressant drug treatment. Blood platelets were collected from 22 drug-free depressed patients and 22 age- and sex-matched healthy controls. The levels of the various G protein subunits were assessed by immunoblotting techniques. The immunoreactivity of G alpha 12 was increased (41%) and that of G alpha i3 decreased (25%) in platelets of depressed patients. The levels of other G protein subunits (G alpha s, G alpha q/11, G beta) did not change significantly with respect to those of control subjects. Chronic administration of cyclic antidepressant drugs (citalopram, clomipramine, imipramine) decreased the immunoreactivity of the up-regulated G alpha i2 protein (31%). Since platelet G alpha i2 is in line with the existence of supersensitivity of these receptors in major depression.

Adult↗

PubMed1997

Marked decrease of immunolabelled 68 kDa neurofilament (NF-L) proteins in brains of opiate addicts.

NEUROFILAMENT (NF) proteins, the major components of the neuronal cytoskeleton, have been shown to represent previously unknown targets for the chronic effects of morphine in rats. This study was designed to evaluate the abundance of immunoreactive NF-L (68 kDa) proteins in post-mortem brains of chronic opiate addicts who had died of a heroin or methadone overdose. Levels of NF-L proteins were assessed by immunoblotting techniques. Levels of immunoreactive NF-L proteins were markedly decreased (47%, n = 17) in the frontal cortex. The reduced abundance of brain NF-L proteins was not related to the post-mortem delay or to the plasma concentrations of opiates, suggesting that the observed changes represent a specific long-term effect of opiate drugs. Because of the functions associated with NF proteins (e.g. axonal transport), this finding suggests that opiate drugs may induce neuronal damage after chronic abuse in humans.

Adult↗

PubMed1997

Regulation of immunolabelled mu-opioid receptors and protein kinase C-alpha and zeta isoforms in the frontal cortex of human opiate addicts.

To assess the status of opioid receptors in the human brain during the process of opiate addiction, the abundance of immunoreactive mu-opioid receptors was quantitated in postmortem brains of chronic opiate addicts who had died of a heroin or methadone overdose. The immunoreactive levels of the associated enzyme protein kinase C (PKC-alpha and zeta isoforms) and G proteins (G alpha(i1/2) subunits) were also assessed in the same brains. In the frontal cortex of opiate addicts, the abundance of mu-opioid receptors was not different from that obtained in matched controls. The level of Ca2+-dependent PKC-alpha was decreased (25%), whereas that of the atypical PKC-zeta remained unchanged. The density of G alpha(i1/2) proteins also was found to be increased (40%). The results indicate that opiate addiction in humans does not appear to be associated with a reduced density of brain mu-opioid receptors. The sustained down-regulation of PKC-alpha in the brain of opiate addicts would allow the up-regulation of G alpha(i1/2) proteins aimed at compensating the postulated desensitization of the mu-opioid receptor system.

Adolescent↗

PubMed1996

Platelet imidazoline receptors and regulatory G proteins in patients with major depression.

The newly discovered imidazoline receptors have been found to be upregulated in patients with major depression (platelet 45 kDa and 35 kDa proteins) and in suicide victims (brain 45 kDa protein). The signalling pathways coupled to these receptors are not known however. The aim of this study was to quantify, in platelets of depressed patients, the density of various G proteins to assess possible associations with the abundance of imidazoline proteins. There were positive correlations between the immunoreactivities of 45 kDa imidazoline receptors and those of G alpha q/11 (r = 0.64, n = 19, p < 0.005), G alpha i2 (r = 0.46, n = 22, p < 0.05) and G beta (r = 0.62, n = 18, p < 0.01) proteins. The relationship with regulatory G alpha q/11 proteins suggests that this 45 kDa protein (putative I1 imidazoline receptor) may couple to phosphoinositide pathway in platelets. This finding might be of relevance in understanding the functional implications of the abnormal higher expression of imidazoline receptors (45 kDa protein) in the pathogenesis of major depression.

Adult↗

PubMed1996

Immunodetection and quantitation of imidazoline receptor proteins in platelets of patients with major depression and in brains of suicide victims.

BACKGROUND: Imidazoline receptors are a newly discovered family of receptors, some of which, like alpha 2-adrenoceptors, have a presynaptic inhibitory effect on the release of norepinephrine. The aim of this study was to identify by immunodetection imidazoline receptor proteins in human platelets and the brain to assess their status in depression and suicide. METHODS: Platelets were collected from 26 drug-free depressed patients and 26 controls. Specimens of frontal cortex (Brodmann area 9) were collected from 13 suicide victims and 11 controls. Levels of imidazoline receptor proteins were assessed by immunoblotting techniques. Solubilized imidazoline receptors were separated by gel electrophoresis, transferred to nitrocellulose membranes, labeled with a specific anti-imidazoline receptor antiserum, and quantitated by image analysis. RESULTS: Platelet and brain membranes expressed similar 45-kd imidazoline receptor proteins, and their mean +/- SEM immunoreactivities were found to be increased in depressed patients (platelets, 40% +/- 5%) and suicide victims (brain, 51% +/- 14%). Platelets also expressed a 35-kd imidazoline receptor protein that was also found to be up-regulated in depressed patients (21% +/- 4%). In contrast, brain membranes did not express this 35-kd protein but revealed a 29/30-kd imidazoline receptor protein that was found to be down-regulated in suicide victims (19% +/- 3%). In a subset of depressed patients who underwent antidepressant treatment, a change in the immunoreactivity of the up-regulated 45-kd platelet imidazoline receptor protein (-35% +/- 5%), but not of the 35-kd protein, was observed. CONCLUSION: 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.

Adult↗