Changes in either the phosphorylation state or the levels of some cAMP-dependent phosphoproteins were also reported 20, 23 - 29 following treatment with these medications.ĭata from clinical investigations suggest disturbances of the cAMP-dependent phosphorylation system in patients with bipolar disorder. Furthermore, alterations in the levels of PKA have been reported 22 after lithium treatment. 13 - 16 Preclinical studies 17 - 22 have shown that the binding of cAMP to regulatory subunits and the activity of PKA are altered after the administration of antidepressant medications and lithium salts. The binding of cAMP to a regulatory subunit dimer results in the release and concomitant activation of the catalytic moieties, which in turn are able to phosphorylate specific substrate proteins, thereby regulating a great variety of cellular functions. 13 - 16 As shown in Figure 1, the PKA holoenzyme is organized as an inactive tetrameric complex composed of a regulatory subunit dimer and 2 monomeric catalytic subunits. The cAMP-dependent protein kinase (protein kinase A ) is a central component of cAMP signaling cascade because, with few exceptions, the intracellular events mediated by cAMP occur through its activation. In recent years, however, numerous studies 2 - 12 have reported abnormalities in components of cyclic adenosine monophosphate (cAMP) signaling such as G proteins in postmortem brain and peripheral cells of patients with bipolar disorder. 1 The biochemical mechanisms underlying the pathogenesis of this disorder remain to be clearly established. These findings may provide clues toward understanding the involvement of cAMP signaling in the pathogenesis of bipolar disorder.īIPOLAR DISORDER is a common illness affecting approximately 1% of the population. The immunolabeling of Rap1 was significantly higher ( P<.001) in untreated euthymic, depressed, and manic patients than in healthy persons.Ĭonclusions Levels of Rap1 and the catalytic subunit of cAMP-dependent protein kinase are altered in the platelets of bipolar patients. No significant differences were found in the immunolabeling of the regulatory subunits (type I and type II) of cAMP-dependent protein kinase. Results The immunolabeling of the catalytic subunit of cAMP-dependent protein kinase was significantly different among groups ( P<.001), with higher values in untreated depressed and manic patients with bipolar disorder compared with untreated euthymic patients with bipolar disorder and healthy subjects. The levels of cAMP-dependent protein kinase and Rap1 were assessed by Western blot analysis, immunostaining, and computer-assisted imaging. Methods Platelets were collected from 112 drug-free patients with bipolar disorder (52 euthymic, 29 depressed, and 31 manic) and 62 healthy subjects. We evaluated the immunoreactivity of the regulatory and catalytic subunits of cAMP-dependent protein kinase (protein kinase A) and 1 of its substrates, Rap1, in platelets from untreated euthymic, manic, and depressed patients with bipolar disorder and healthy subjects. Shared Decision Making and Communicationīackground Abnormalities in the cyclic adenosine monophosphate (cAMP)–dependent phosphorylation system have been recently reported in patients with bipolar disorder.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.Clinical Implications of Basic Neuroscience.Challenges in Clinical Electrocardiography.
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