Alpha2-adrenoceptor levels on platelets of patients with major depressive disorders

Carstens, Machteld E.; Engelbrecht, A. H. P.; Russell, Vivienne A.; Aalbers, Cor; Gagiano, C. A.; Chalton, D. O.; Taljaard, J. J. F.

doi:10.1016/0165-1781(86)90017-x

Cited by 38 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results with intact platelets agree with earlier studies (Stump and Macfarlane, 1983;Macfarlane et al, 1981). Similarly, previous reports of 3H-clonidine or 3H-PAC binding to platelet lysate particulates have shown moderate binding, and clearly above that observed for intact platelets (Stump and Macfarlane, 1983;Shattil et al, 1981;Carstens et al, 1986) (Figs. 1, 2).…”

Section: Discussionsupporting

confidence: 95%

“…Our 3H-PAC binding to platelet lysate particulates displayed a somewhat lower percent specific binding (35%) than most previous reports. Other investigators have reported 30-50% specific binding (Steer and Atlas, 1982), 40-70% specific binding (Shattil et al, 1981), and 46-50% specific binding (Carstens et al, 1986). Two studies did not report the percent specific binding (U 'Prichard, 1981;Georgotas et al, 1987).…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Comparison of3H-para-aminoclonidine binding to different platelet preparations

Piletz

Halaris

1990

J. Neural Transmission

View full text Add to dashboard Cite

The binding to human platelets of 3H-para-aminoclonidine (3H-PAC), an alpha2 adrenoceptor partial agonist, appears to be altered in depressed patients. We observed that the parameters of 3H-PAC binding to purified plasma membranes from platelets of normal Red Cross volunteers, compare favorably to those reported for binding to normal human autopsy prefrontal cortical lysates. However, only purified plasma membranes from platelets yielded a close comparison. 3H-PAC binding to intact platelets from healthy volunteers was less than 10% displaceable by an alpha2 adrenoceptor antagonist and was therefore unquantifiable. A low percent of specific binding (approx. 35%) was also observed in washed platelet lysates, and the binding was not of very high affinity (KD greater than 10 nM). In contrast, the binding of 3H-PAC to platelet purified plasma membranes from healthy subjects displayed two high affinity binding sites (KD1 = 10.6 pM and KD2 = 1.2 nM). These results are discussed in relation to our recent finding of elevated 3H-PAC binding to platelet purified plasma membranes from depressed patients as compared to healthy subjects.

show abstract

Section: Discussionsupporting

confidence: 95%

Section: Discussionmentioning

confidence: 90%

Comparison of3H-para-aminoclonidine binding to different platelet preparations

Piletz

Halaris

1990

J. Neural Transmission

View full text Add to dashboard Cite

show abstract

“…The mechanism whereby the G protein function decreased must be looked for elsewhere, for instance in the agonist stimulation. Several independent groups, but not all (Garcia-Sevilla et al, 1986; Piletz et al, 1990) have shown that different a2-AR-agonists such as clonidine, p-amino-donidine or bromoxidine decreased the affinity to the platelet a2-AR in depressed patients, despite increased a2-AR density (Carstens et al, 1986;Takeda et al, 1989;Karege et al, 1991;Kaneko et al, 1992). This decreased affinity could probably explain why, in spite of increased G protein level, their function as assessed by the a2-AR-mediated GTPyS binding was lessened.…”

Section: Discussionmentioning

confidence: 95%

Change in platelet GTP-Binding protein in drug-free depressed patients

Karege

Bovier

Stepanian

et al. 1996

Hum. Psychopharmacol. Clin. Exp.

View full text Add to dashboard Cite

2 chemin du Petit Bel-Air, CH-I22S Chsne-Bourg. Geneva, SwitzedandIn order to examine the status of cell signal transduction in depression, we measured in the same subjects both the platelet guanine nucleotide binding protein (G protein) levels and G protein function in drug-free depressed patients. G protein levels were measured thanks to the method of Western immunoblot of three G protein subunits, i.e. Gai2; Gaq and GP. The G protein function was assessed by the method of GTPyS binding through platelet a2-adrenoceptor stimulation. The results showed an increase in immunoreactivity of the three G proteins in major depressed patients. The study of GTPyS binding on platelet membrane showed a significant decrease in drug-free depressed patients with respect to age-and gender-matched controls. These data suggest that uncoupling of a2-adrenoceptor from G proteins, whose levels were increased, may be found in depression.

show abstract

“…A number o f reports have found an augmented density of ob-adrenoceptors, but these newly formed receptors were considered to be either poorly coupled to the effector or not functionally active [10-12, 14], In contrast, decrease of tb-adrenoceptor affinity observed with different agonists, such as 3H-clonidine [13], 3H-p-aminoclonidine [19] or 3H-UK 14304 [12. 14] was considered more important for the receptor function [14], Furthermore, activation of Cbadrenoceptor-mediated AC inhibition which was found to be decreased in depression [11] suggests impairment in the signal transduction process, although the relation between platelet aggregation and AC inhibition was ques tioned [20], Finally, what could be the significance of such an abnormality in the platelet cb-adrenoceptor?…”

Section: Discussionmentioning

confidence: 99%

Adrenaline-Induced Platelet Aggregation in Depressed Patients and Control Subjects

Karege¹,

Bovier²,

Hilleret³

et al. 1993

Neuropsychobiology

View full text Add to dashboard Cite

We measured α₂-adrenoceptor-mediated platelet primary aggregation in depressed patients and healthy subjects. Both initial velocity and maximum amplitudes of platelet response to increasing concentrations of adrenaline were decreased in drug-free depressed patients as compared with controls. The EC₅₀ of both initial slope and maximum amplitude were also increased in drug-free depressed patients. The results suggested a lowered platelet α₂-adrenoceptor function. Demographic factors (age and sex) and the time between blood collection and start of aggregation monitoring did not influence the results. This report is consistent with postsynaptic receptor desensitization in depressed patients. The precise molecular mechanism for this impairment remains to be elucidated.

show abstract

Alpha2-adrenoceptor levels on platelets of patients with major depressive disorders

Cited by 38 publications

References 27 publications

Comparison of3H-para-aminoclonidine binding to different platelet preparations

Comparison of3H-para-aminoclonidine binding to different platelet preparations

Change in platelet GTP-Binding protein in drug-free depressed patients

Adrenaline-Induced Platelet Aggregation in Depressed Patients and Control Subjects

Contact Info

Product

Resources

About