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1.
Platelet alpha 2 binding was measured in 14 patients with panic attacks and 21 controls using the antagonist 3H-rauwolscine as radioligand. The mean (+/- SD) Bmax values of patients (116 +/- 45 fmoles/mg protein) and controls (106 +/- 32 fmoles/mg protein) was not significantly different (p greater than 0.05, Mann-Whitney U test). There was a nonsignificant trend for the Kd of patients (1.25 +/- 0.67 nM) to be higher than that of controls (0.96 +/- 0.32 nM). The results do not support an adrenergic abnormality in panic patients. 相似文献
2.
Binding parameters (Bmax and Kd) of alpha 2-adrenergic receptors were studied in platelets from 14 depressed patients and 18 control subjects. Using 3H-clonidine (a partial alpha 2-adrenergic agonist) as the ligand and membranes, prepared from platelets isolated under physiological conditions, we found no significant differences in Bmax and Kd between medication free patients and control subjects. Platelet binding parameters in the depressed patients did not correlate with plasma levels of norepinephrine, epinephrine or MHPG. Age had a significant positive effect on platelet alpha 2-adrenergic receptor Bmax in both groups, and may have masked the patient-control differences. Treatment with desipramine for 28 days had no effect on the binding parameters in depressed patients when compared to pretreatment values. Adding desipramine to platelets of control subjects 'in vitro' did also not affect binding parameters. Our findings suggest that receptor binding studies with a partial alpha 2-adrenergic agonist in platelet membranes are not a useful model to test the hypothesis of a central supersensitive adrenergic system in depression. 相似文献
3.
To examine whether alpha 2-adrenergic receptor function is altered in affective and schizophrenic disorders, we determined 3H-clonidine binding in platelets obtained from 33 normal control subjects and from 24 patients with depressive, 22 patients with schizophrenic, 18 with bipolar, and 8 patients with schizoaffective disorders during a drug-free period. The maximum number of binding sites (Bmax) and apparent dissociation constant (Kd) for high affinity 3H-clonidine binding was computed by Scatchard analysis. Comparison of the diagnostic groups indicated that the Bmax in depressed, schizophrenic, and schizoaffective patients was significantly higher than in normal controls, but there were no significant Bmax differences between bipolar patients and controls. Comparison of the Kd among the diagnostic groups indicated no significant differences among the groups or between patient diagnostic groups and normal controls. Baseline Bmax in schizophrenic patients was significantly correlated with the decrease in Brief Psychiatric Rating Scale (BPRS) scores after treatment, suggesting a relationship between baseline Bmax and clinical response. Treatment with lithium caused a significant decrease in the baseline Bmax, whereas treatment with desipramine or trifluoperazine did not cause significant changes in the baseline Bmax. Our results thus indicate an increase in the number of alpha 2-adrenergic receptors in depressed and schizophrenic patients as compared to normal controls. 相似文献
4.
J A García-Sevilla A P Zis P J Hollingsworth J F Greden C B Smith 《Archives of general psychiatry》1981,38(12):1327-1333
The specific binding of tritiated (3H)-clonidine, an alpha 2-adrenergic receptor agonist, to platelet membranes was measured in normal subjects and in patients with major depressive disorder. The number of platelet alpha 2-adrenergic receptors from the depressed group was significantly higher than that found in platelets obtained from the control population. Treatment with tricyclic antidepressant drugs led to significant decreases in the number of platelet alpha 2-adrenergic receptors. These results support the hypothesis that the depressive syndrome is related to an alpha 2-adrenergic receptor supersensitivity and that the clinical effectiveness of tricyclic antidepressant drugs is associated with a decrease in the number of these receptors. 相似文献
5.
The platelet membrane was used as a model system to examine alpha 2-adrenergic receptors in 30 depressed patients and 30 healthy control subjects. The number of binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were assayed in the same sample. A decreased agonist-receptor affinity was found in depressed patients, whereas receptor density was not significantly altered compared with that in control subjects. In bipolar depressed and dysthymic patients, there was a tendency toward a higher density of alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent depressed subjects. Moreover, a positive correlation between Bmax and Kd values was observed in patients but not in control subjects--a finding that suggests that a compensatory phenomenon occurs in depression. After the patients were treated with antidepressant drugs, an increased affinity (decrease in Kd) was observed, together with a decrease in binding sites. Plasma magnesium concentrations were higher in drug-free depressed patients than in control subjects. In addition, magnesium concentrations were negatively correlated with the density of alpha 2-adrenergic receptor binding sites in depressed patients, both before and during treatment. Lastly, a trend toward a negative correlation between plasma MHPG concentration and the number of binding sites was also observed. These results suggest a complex multifactorial regulation of alpha 2-adrenergic receptors, which are probably hyposensitive in depressive syndromes. 相似文献
6.
Platelet alpha 2-adrenergic receptor binding sites in major depressive disorder and borderline personality disorder 总被引:1,自引:0,他引:1
Platelet alpha 2-adrenergic receptor binding sites were measured in a group of patients with major depressive disorder (MDD) (n = 23) and in normal controls (n = 25). When all depressed subjects were compared to controls, there were no differences in either Kd (affinity of the ligand) or total binding site (number/platelet), although a significant change in the ratio of high to low affinity states was observed in the depressed group. When the depressed patients were subdivided into those with and without a co-occurring borderline personality disorder (BPD), the BPD group had significantly fewer alpha 2 high affinity binding sites, while the group with depression alone had significantly more binding sites (both low and high affinity) than the control group. The results support the concept that assessment of comorbid diagnoses may be essential to biological studies of depression. 相似文献
7.
Transient cerebral ischemia results in selective neuronal cell death. The mechanisms underlying this selective vulnerability to ischemia are only beginning to be elucidated. We studied the effect of ischemia on alpha 1-adrenergic receptor binding by measuring [3H]prazosin binding in gerbil forebrain membranes after 10 min of bilateral carotid occlusion. Binding was reduced from 62 +/- 3 to 33 +/- 4 fmol/mg protein. Binding in the same membranes to beta 2-adrenergic receptors were also decreased, but not to the extent of that to alpha 1-adrenergic receptors. Binding to muscarinic cholinergic [( 3H]quinuclydil benzilate) and beta 1-adrenergic receptors were only slightly depressed. Surprisingly, the protein content was significantly increased in the membrane fraction studied from ischemic forebrain (68 +/- 4 mg/g wet weight) compared with sham operated controls (57 +/- 4). The dramatic decrease in alpha 1-adrenergic receptor binding during ischemia is consistent with receptor binding studies of membranes pretreated with phospholipase A2 in vitro. It is not clear what effect this change in alpha 1-adrenergic receptor binding has on subsequent selective neuronal death. The recent demonstration that catecholamines and locus ceruleus neurons influence the loss of CA1 neurons in the hippocampus suggests that it may play an important modulatory role. 相似文献
8.
The binding of 3H-dihydroergocryptine and 3H-yohimbine to intact, discoid, functional, washed human platelets resuspended in Tyrode's buffer containing Ca2+, Mg2+, human albumin and apyrase, was studied at 37 degrees C. The binding of 3H-dihydroergocryptine was rapid, reversible and saturable (KD = 19.3 +/- 4.2 nM, Bmax = 2590 +/- 670 sites per platelet). The results were difficult to interpret because the bound ligand was not easily dissociated. In contrast, 3H-yohimbine bound in a rapid, reversible and saturable fashion to one class of sites (KD = 8.1 +/- 1 nM, Bmax = 395 +/- 35 sites/platelet) with the characteristics of alpha 2-adrenergic receptors. Adrenaline alone did not aggregate intact platelets but potentiated ADP-induced aggregation. This effect of adrenaline was specifically inhibited by alpha 2-antagonists such as yohimbine. The inhibition of 3H-yohimbine binding and the inhibition of the synergistic effect of adrenaline on ADP-induced aggregation by 16 different alpha- and beta-adrenergic compounds was significantly correlated (p less than 0.001). Thus, intact and functional washed human platelets can be used as a simple pharmacological model to screen alpha-adrenergic antagonists by measuring the inhibition of the potentiation of ADP-induced aggregation by adrenaline which is a direct reflection of the physiological effect of adrenaline on human platelet alpha 2-adrenergic receptors. The inhibition constant derived from aggregation studies expresses the affinity of the ligand for its receptor as measured by more cumbersome binding studies with radioactive adrenergic antagonists such as 3H-yohimbine. 相似文献
9.
We have investigated the functioning of alpha 2-adrenergic receptors in patients with major depressive disorder by measuring the specific binding of 3H-yohimbine, an alpha 2-adrenergic receptor antagonist, to platelet membranes. Bmax and Kd values for platelet 3H-yohimbine binding were normal in unmedicated patients with major depressive disorder, and did not correlate with scores on the Hamilton rating scale for depression. Platelet alpha 2-adrenergic antagonist sites were also unchanged in number or affinity in depressed patients after long-term treatment with a variety of antidepressant medications. 相似文献
10.
Brigitta Bondy Manfred Ackenheil Rembert Elbers Manfred Fröhler 《Psychiatry research》1985,15(1):41-48
The specific binding of the dopamine antagonist 3H-spiperone to lymphocytes from a healthy control group (n = 40), a group of acute, unmedicated schizophrenic patients (n = 27), and a psychiatric control group (n = 16) was investigated. There were no differences in binding parameters between the healthy controls (Bmax 2.6 +/- 0.7 fmoles/10(6) cells; Kd 0.17 +/- 0.07 nM) and the psychiatric control group. Binding capacity of 3H-spiperone was significantly increased in lymphocytes from the schizophrenic patients (Bmax 14.4 +/- 9.3 fmoles/10(6) cells). Moreover, a slight decrease in affinity was observed (Kd 0.44 +/- 0.21 nM). Because the increase in binding appeared only in schizophrenic patients, this peripheral model could prove valuable as a diagnostic criterion. 相似文献
11.
L J Siever T W Uhde D C Jimerson M S Kafka C R Lake S Targum D L Murphy 《Progress in neuro-psychopharmacology & biological psychiatry》1983,7(2-3):249-261
Pre-clinical and clinical studies suggest that the responsiveness of monoamine and cholinergic receptors may be altered in the affective disorders and that antidepressants may modify the sensitivity of these receptors. The growth hormone response to clonidine is reduced in depressed patients compared to controls according to several independent studies, suggesting that post-synaptic alpha 2-adrenergic receptors may be less responsive in depressed patients. The cortisol response to clonidine is enhanced in depressed patients compared to controls in our study raising the possibility that cortisol hypersecretion in depressed patients may be related to noradrenergic dysfunction. The hypotensive response to clonidine is blunted in patients on chronic antidepressant treatment with either clorgyline or desipramine suggesting that pre-synaptic alpha 2-adrenergic receptors may subsensitize with chronic antidepressant treatment. The prolactin increase in response to fenfluramine is less in depressed patients compared to controls suggesting decreased functional activity of the serotonergic system in depression. Platelet alpha 2-adrenergic receptor number as measured by tritiated dihydroergocriptine (3H-DHE) binding is increased in depressed patients compared to controls, while cyclic 3'-5' adenosine monophosphate (cAMP) production in response to prostaglandin E1 (PGE1) and norepinephrine (NE) inhibition of PGE1-stimulated cAMP production are reduced in the platelets of depressed patients. Thus, it is not clear that increased 3H-DHE binding reflects increased functional responsiveness and might in fact be compensatory to decreases in functional responses of alpha 2-adrenergic receptors. 相似文献
12.
Controversy exists regarding the relationship between anxiety states and major depression. We studied the binding of tritiated imipramine to platelet membranes in order to determine if patients with agoraphobia and panic attacks differed from depressed subjects or healthy volunteers on this biological parameter. Mean (+/- SD) Bmax and Kd values were significantly lower in patients with agoraphobia and panic attacks (787 +/- 276 fmole/mg protein and 0.35 +/- 0.14 nM, respectively) than in healthy volunteers (1237 +/- 201 fmole/mg protein and 0.71 +/- 0.37 nM, respectively). In addition, patients with agoraphobia and panic attacks had binding parameters that were similar to those of patients with bipolar or familial pure depressive disorder, but significantly lower than those of patients with depressive spectrum or sporadic depressive disorder. These findings have implications for both the nosology and pathophysiology of anxiety disorders. 相似文献
13.
Mouse brain astrocytes from primary cultures were found to contain both alpha 1 and alpha 2 adrenergic receptors. 3H WB 4101 labeled one category of binding site (KD = 1.5 +/- 0.39 nM, Bmax = 64 +/- 7.9 fmoles/mg protein) with typical alpha 1 adrenergic specificity (WB 4101 greater than prazosin greater than yohimbine). The density of alpha 1 adrenergic receptors was 2-3 times higher in mouse cerebral cortex than in glial cells. Like rat brain [U'Pritchard et al, 1979; Rouot et al, 1980], mouse glial cells were found to contain two categories of 3H clonidine binding sites: high affinity sites, which were identical to the high but not to the low affinity sites found in rat brain, since 1) they displayed the same affinity for 3H clonidine (KD = 1.2 +/- 0.13 nM, n = 4) and the same typical alpha 2 adrenergic specificity (yohimbine greater than WB 4101 greater than prazosin); 2) the dissociation rate constant for clonidine binding was equal to 0.06 min-1, a value close to that found previously for the high affinity 3H clonidine binding sites in rat brain (0.05 min-1); and 3) divalent cations augmented and guanyl nucleotides reduced 3H clonidine binding as in rat brain. Na+ decreased 3H clonidine binding in a complex manner. The number of high affinity sites in glial cells (52 +/- 9.4 fmoles/mg protein, n = 4) was half the number found in mouse cerebral cortex (98 fmoles/mg protein). Low affinity 3H clonidine binding sites (KD = 81 +/- 18 nM, Bmax = 96 +/- 5.8 fmoles/mg protein, n = 3) were not fully characterized. In conclusion, glial cells contained the same alpha adrenergic receptors as those described in brain, but their physiological function is not yet known. 相似文献
14.
Abnormalities in the serotonergic system have been implicated in the pathophysiology of depressive disorders. Human platelets possess serotonin-2A (5-HT(2A)) receptors, and previous research using LSD or ketanserin as ligands have indicated that their number is increased in depressed patients. Compared to other ligands previously used in platelet studies, DOI is highly selective for the 5-HT(2A) receptor and binds to its high-affinity state, therefore labeling only the receptors that are biologically coupled to the G-protein. We determined the density (Bmax) and the affinity (Kd) of 5-HT(2A) receptors labeled by [(125)I]-DOI in platelets from 21 untreated patients with major depression and 21 healthy volunteers. The density of the 5-HT(2A) binding sites was found to be increased in platelets from female depressed patients as compared to controls. No changes were observed in the Kd. We did not find any relationship between the binding parameters and either the severity of the depressive episode or the suicidal tendencies of the patients. Our results show that the number of coupled platelet 5-HT(2A) receptors is increased in depressed patients, indicating that platelet 5-HT(2A) receptor function is enhanced in depression. 相似文献
15.
Characterization of platelet alpha 2 adrenoceptors and measurement in control and depressed subjects
I C Campbell R M McKernan S A Checkley I B Glass C Thompson E Shur 《Psychiatry research》1985,14(1):17-31
The alpha-adrenoceptor on platelets has been characterized using 3H-yohimbine, 3H-dihydroergocriptine, and 3H-clonidine. The receptor, which exhibits the characteristics of an alpha 2-type, has a Bmax for dihydroergocriptine of 330 fmoles/mg protein, for yohimbine of 178 fmoles/mg protein, and for clonidine of 38 fmoles/mg protein. Clonidine, but not yohimbine binding, is decreased by the presence of K+, Na+, or Li+. Adenosine triphosphate (ATP) and the guanosine triphosphate (GTP) analogue, Gpp(NH)p, reduce the affinity of clonidine for its binding site. Acute exercise, such as playing squash, does not apparently alter the Bmax or Kd of 3H-yohimbine binding to platelet membranes, and in vitro studies, with intact platelets or platelet membranes, show that incubation with adrenalin (10 microM) does not induce alterations in Bmax or Kd. In the present study, no correlation was found between age and alpha 2-adrenoceptor numbers. There was no significant difference in the Bmax for 3H-yohimbine binding to platelet membranes from control and depressed subjects, although the mean value for the depressed group was some 10% lower than that for the corresponding control group. There were no overall significant and consistent effects of desipramine (DMI) treatment. After 2-3 days of treatment, the Bmax was reduced by 20%, after 7 days by 14%, and after 21 days it was 8% above the control value. When an additional group of patients on DMI (7 days of treatment) was analyzed using one supramaximal concentration of 3H-yohimbine, there was a significant decrease (25%) in binding. 相似文献
16.
We have recently established that canine narcolepsy (an autosomal recessive genetic model of the human disorder) is dramatically improved by treatment with alpha 2 antagonists such as yohimbine (Nishino et al: J Pharmacol Exp Ther 253:1145-1152, 1990). To further investigate the role of alpha 2 adrenoceptors in narcolepsy, receptors labeled with [3H] yohimbine were examined on platelets from human and canine narcoleptic subjects. Twenty-eight Doberman pinschers were studied, 7 controls (C), 7 heterozygous (Hz), and 14 narcoleptics (N) (age and sex matched), including eight animals born in a backcross setting (narcoleptic x heterozygous; 5 narcoleptics and 3 heterozygous). The Kd and Bmax of each group respectively, were as follows: C, Kd = 2.86 +/- 0.76 nmol/L, Bmax = 295.78 +/- 31.89 fmol/mg protein; Hz, Kd = 2.06 +/- 0.23 nmol/L, Bmax = 307.02 +/- 22.21 fmol/mg protein; and N, Kd = 2.72 +/- 0.45 nmol/L, Bmax = 267.52 +/- 19.47 fmol/mg protein. No statistical differences were found between groups using nonparametric (Kruskall-Wallis) statistical procedures, and there were no correlations between any binding parameter and symptom severity within the narcoleptic group. Platelet alpha 2 receptor affinity and density also did not differ between narcoleptic and heterozygous dogs in the backcross litter (N [n = 5], Kd = 1.94 +/- 0.59 nmol/L, Bmax = 290.6 +/- 64.7 fmol/mg protein; Hz [n = 3], Kd = 2.83 +/- 0.47 nmol/L, Bmax = 294.2 +/- 42.9 fmol/mg protein). Fourteen human subjects, seven control and seven narcoleptic patients (age and sex matched), were included in the study.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
17.
Alpha 2-adrenoceptor levels on platelets of patients with major depressive disorders 总被引:1,自引:0,他引:1
M E Carstens A H Engelbrecht V A Russell C Aalbers C A Gagiano D O Chalton J J Taljaard 《Psychiatry research》1986,18(4):321-331
3H-p-Aminoclonidine binding to platelets of patients with primary, unipolar major depressive disorder was compared to that of a normal healthy control population. The variances of platelet alpha 2-adrenoceptor Kd and Bmax values in patients were significantly greater than in the control group. No significant difference could be demonstrated between the Kd values of the two different groups, but the Bmax value of the depressed group was significantly lower than that of controls. We propose that an abnormal platelet alpha 2-adrenoceptor density may be used as a biological marker for major depressive disorder. 相似文献
18.
The endocannabinoid 2-arachidonoylglycerol (2-AG) has been shown to activate human platelets in platelet-rich plasma, by binding to a "platelet-type" cannabinoid receptor (CB(PT)). Here, washed human platelets were used to characterize the binding of [(3)H]2-AG to CB(PT), showing a dissociation constant (Kd) of 140 +/- 31 nM and a maximum binding (Bmax) of 122 +/- 10 pmol.mg protein(-1). Selective antagonists of both CB1 and CB2 cannabinoid receptors inhibited this binding, which was enhanced up to approximately 230% over the controls by 1 micro M serotonin (5-hydroxytryptamine, 5-HT). Human platelets were also able to bind [(3)H]5-HT (Kd = 79 +/- 17 nM, Bmax = 14.6 +/- 1.3 pmol.mg protein(-1)), and 1 micro M 2-AG enhanced this binding up to approximately 150%. Moreover, they were able to take up [(3)H]5-HT through a high affinity transporter (Michaelis-Menten constant = 22 +/- 2 nM, maximum velocity = 344 +/- 15 pmol.min(-1).mg protein(-1)), which was not affected by 2-AG. Interestingly, 5-HT did not affect the activity of the 2-AG transporter of human platelets. Treatment of washed platelets with 1 micro M 2-AG led to increased intracellular inositol-1,4,5-trisphosphate (up to approximately 300%) and decreased cyclic AMP (down to approximately 50%). Furthermore, treatment of pre-loaded platelets with 1 micro M 2-AG induced a approximately 300% increase in [(3)H]2-AG release, according to a CBPT-dependent mechanism. Also, 1 micro M 5-HT enhanced the effect of 2-AG on inositol-1,4,5-trisphosphate ( approximately 500% of the controls), cyclic AMP ( approximately 20%) and [(3)H]2-AG release ( approximately 570%), and the latter process was shown to be partly ( approximately 50%) involved in the 5-HT-dependent platelet activation. Taken together, reported findings represent the first demonstration that 2-AG and 5-HT can mutually reinforce their receptor binding on platelet surface, which might have therapeutic implications. 相似文献
19.
P J Ambrosini C Metz R C Arora J C Lee L Kregel H Y Meltzer 《Journal of the American Academy of Child and Adolescent Psychiatry》1992,31(2):298-305
Kinetic constants of platelet imipramine binding were determined in youths with major depression, and a contrast group. Subjects actively depressed (N = 10) had significantly fewer imipramine binding sites (Bmax) (877 +/- 148 fmol/mg protein) than recovering depressives (N = 12) (1220 +/- 428 fmol/mg protein) and contrasts (N = 10) (1270 +/- 230 fmol/mg protein). Affinity constants (Kd) (1.14 +/- 0.36 nM, 0.97 +/- 0.31 nM, and 1.17 +/- 0.39 nM, respectively) were similar among the groups. Actively depressed males but not females had fewer imipramine binding sites than both their sex-matched comparison groups. Although actively depressed females' Bmax was significantly lower than recovering depressed and nondepressed males, neither age, Tannner stage, nor circannual rhythms influenced Bmax, but suicidality may be associated with low Bmax. A decrease in Bmax may be a state-specific marker of major depression in boys or associated with a depressive disorder with a suicidal history. 相似文献
20.
Increased 5-HT-2 receptor function as measured by serotonin-stimulated phosphoinositide hydrolysis in platelets of depressed patients. 总被引:2,自引:0,他引:2
M Mikuni I Kusumi A Kagaya Y Kuroda H Mori K Takahashi 《Progress in neuro-psychopharmacology & biological psychiatry》1991,15(1):49-61
1. The present study was undertaken to examine whether or not 5-HT-induced inositol monophosphate (IP-1) accumulation in human platelets is mediated by 5-HT-2 receptors and to assess 5-HT-2 receptor function as measured by 5-HT-stimulated IP-1 accumulation in platelets from normal controls and depressed patients before drug treatment. 2. In platelets prelabeled with 3H-myo-inositol, in Ca ion free HEPES buffer containing 10 mM LiCl, 5-HT caused a dose-dependent accumulation of IP-1 during 15 min incubation. A maximal increase in IP-1 formation was observed at 30 microM of 5-HT and its EC50 value was 4 microM. 3. Ketanserin, a selective 5-HT-2 antagonist, was a potent inhibitor of 5-HT-stimulated IP-1 accumulation with a Ki value of 12 nM, but (-)propranolol (10 microM), a 5-HT-1 antagonist, failed to block the 5-HT response. 4. The potencies of various compounds tested to inhibit 5-HT-stimulated IP-1 accumulation in human platelets correlated positively with the affinities to 5-HT-2 receptor as defined by radioligand binding in rat cerebral cortex. 5. In a group of unmedicated patients with major depressive disorder matched for age with normal control group, we found a significant increase in 5-HT (100 microM)-induced accumulation of IP-1 (150 +/- 7% of basal for depressed patients, 132 +/- 3% for controls). 相似文献