Platelet alpha2A-adrenoceptor function in major depression: Gi coupling, effects of imipramine and relationship to treatment outcome

Regulation of Platelet α2A-Adrenoceptors, Gi Proteins and Receptor Kinases in Major Depression: Effects of Mirtazapine Treatment

“…The results of the first part of the study indicate the existence of an increased density of the a 2A -adrenoceptor/ Gai protein complex in blood platelets of drug-free depressed patients, which is in agreement with previous reports in postmortem brains (Callado et al, 1998;García-Sevilla et al, 1999;Ordway et al, 2003) and platelets , 1986, 1987, 1990Piletz et al, 1991;Gurguis et al, 1999) from depressed subjects. Therefore, these results further support the existence of supersensitive a 2A -adrenoceptors in major depression (Fu et al, 2001;González-Maeso et al, 2002; see also Flügge et al, 2003).…”

“…Therefore, the observed clinical efficacy and downregulation of a 2A -adrenoceptors induced by mirtazepine also support a relevant role of supersensitive a 2A -adrenoceptors in the pathogenesis of major depression (Fu et al, 2001;González-Maeso et al, 2002). Chronic antidepressant treatments have been repeatedly shown to induce downregulation and desensitization of a 2 -adrenoceptors and/or Gai proteins in the platelets of depressed patients (García-Sevilla et al, 1986, 1987, 1990Piletz et al, 1991;Gurguis et al, 1999), and in the rat Barturen and García-Sevilla, 1992;Kovachich et al, 1993;Mongeau et al, 1994;Esteban et al, 1999;Mateo et al, 2001) and human (De Paermentier et al, 1997;García-Sevilla et al, 1999) brains. Similar to other antidepressant drugs, mirtazapine could also induce the downregulation of platelet a 2 -adrenoceptors, indirectly, through the rise in plasma norepinephrine induced by the drug.…”

“…Chronic psychosocial stress in monkeys (a model of depression) has also been shown to induce persistent increases of a 2A -adrenoceptors in the brain (Flügge et al, 2003). Moreover, depressed patients also display upregulation and supersensitive a 2A -adrenoceptors in blood platelets , 1986, 1987, 1990Piletz et al, 1991;Gurguis et al, 1999). These observations suggest that patients with mood disorders might have an underlying disturbance of noradrenergic system, perhaps due to hyperactive a 2 -adrenoceptor function (Fu et al, 2001).…”

Protein Kinase C and Phospholipase C Activity and Expression of Their Specific Isozymes Is Decreased and Expression of MARCKS Is Increased in Platelets of Bipolar but Not in Unipolar Patients

“…Abnormalities in 5HT 2A (Pandey et al 1995), ␣ 2 adrenergic receptors (Pandey et al 1990), G-proteins (Garcia-Sevilla et al. 1997Karege et al 1998;Gurguis et al 1999), and levels of PIP 2 , a substrate for PI-PLC (Brown et al 1993;Soares and Mallinger 1996;Soares et al 1999), have been reported in platelets of unipolar and/or bipolar patients. PLC and PKC are two crucial components of the PI signaling system.…”

“…These abnormalities may be related to abnormalities in receptors, such as 5HT 2A , 5HT 2C , muscarinic M 1 and M 2 , or ␣ 2 adrenergic receptors linked to the PI signaling system or to abnormal levels of substrates, such as PIP 2 , or to components of the signaling cascade, such as G-proteins, PKC, or PLC. Abnormalities in 5HT 2A (Pandey et al 1995), ␣ 2 adrenergic receptors (Pandey et al 1990), G-proteins (Garcia-Sevilla et al 1997;Karege et al 1998;Gurguis et al 1999), and levels of PIP 2 , a substrate for PI-PLC (Brown et al 1993;Soares and Mallinger 1996;Soares et al 1999), have been reported in platelets of unipolar and/or bipolar patients.…”