The lymphoblast β-adrenergic receptor in bipolar depressed patients: characterization and down-regulation

Kay, Gillian; Sargeant, M.; McGuffin, Peter; Whatley, S.; Marchbanks, R. M.; Baldwin, David S.; Montgomery, S.; Elliott, J.M.

doi:10.1016/0165-0327(93)90004-4

Cited by 17 publications

(6 citation statements)

References 32 publications

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“…For example, Young et al (1993) reported that forskolin-stimulated adenylyl cyclase activity is significantly increased in temporal and occipital cortices of bipolar patients compared with normal control subjects. Also Kay et al (1993) reported that PGE 1 -stimulated adenylyl cyclase activity was significantly increased in lymphoblast cell lines of bipolar patients. Klysner et al (1987) observed increased β 2 -AR responsiveness in manic-depressive patients compared with euthymic patients treated with antidepressants.…”

Section: Adenylyl Cyclase and Camp Formation In Mood Disordersmentioning

confidence: 97%

“…Most earlier studies utilized peripheral tissues to examine levels of cAMP or receptor-mediated cAMP formation. For example, it was shown that the baseline level of cAMP in plasma, cerebrospinal fluid (Belmaker et al 1980; Post et al 1982; Maj et al 1984), or in leukocytes or lymphoblast cell lines (Klysner et al 1987; Kay et al 1993), is not altered in various mood states. On the other hand, changes in receptor-mediated cAMP formation were found in these patients.…”

Section: Adenylyl Cyclase and Camp Formation In Mood Disordersmentioning

confidence: 99%

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Adenylyl cyclase-cyclicAMP signaling in mood disorders: Role of the crucial phosphorylating enzyme protein kinase A

Dwivedi

Pandey²

2008

NDT

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Mood disorders are among the most prevalent and recurrent forms of psychiatric illnesses. In the last decade, there has been increased understanding of the biological basis of mood disorders. In fact, novel mechanistic concepts of the neurobiology of unipolar and bipolar disorders are evolving based on recent pre-clinical and clinical studies, most of which now focus on the role of signal transduction mechanisms in these psychiatric illnesses. Particular investigative emphasis has been given to the role of phosphorylating enzymes, which are crucial in regulating gene expression and neuronal and synaptic plasticity. Among the most important phosphorylating enzyme is protein kinase A (PKA), a component of adenylyl cyclase−cyclic adenosine monophosphate (AC−cAMP) signaling system. In this review, we critically and comprehensively discuss the role of various components of AC−cAMP signaling in mood disorders, with a special focus on PKA, because of the interesting observation that have been made about its involvement in unipolar and bipolar disorders. We also discuss the functional signifi cance of the fi ndings regarding PKA by discussing the role of important PKA substrates, namely, Rap-1, cyclicAMP-response element binding protein, and brain-derived neurotrophic factor. These studies suggest the interesting possibility that PKA and related signaling molecules may serve as important neurobiological factors in mood disorders and may be relevant in target-specifi c therapeutic interventions for these disorders.

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Section: Adenylyl Cyclase and Camp Formation In Mood Disordersmentioning

confidence: 97%

Section: Adenylyl Cyclase and Camp Formation In Mood Disordersmentioning

confidence: 99%

Adenylyl cyclase-cyclicAMP signaling in mood disorders: Role of the crucial phosphorylating enzyme protein kinase A

Dwivedi

Pandey²

2008

NDT

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“…For example, Young et al [28] reported that forskolin-stimulated adenylyl cyclase activity is significantly increased in temporal and occipital cortices of bipolar patients compared with normal control subjects. Also Kay et al [52] reported that PGE 1 -stimulated adenylyl cyclase activity was significantly increased in lymphoblast cell lines of bipolar patients. Klysner et al [51] observed increased 2 -AR responsiveness in manic depressive patients compared with euthymic patients treated with antidepressants.…”

Section: Cyclicamp In Mood Disordersmentioning

confidence: 97%

“…Baseline cAMP levels in plasma and cerebrospinal fluid [48][49][50], or in leukocytes or lymphoblast cell lines [51,52], appear to be normal in various mood states. However, the receptor-mediated cAMP response was found to be altered in mood disorders.…”

Section: Cyclicamp In Mood Disordersmentioning

confidence: 99%

The Concept of Dysregulated Signal Transduction and Gene Expression in the Pathophysiology of Mood Disorders

Dwivedi¹

2005

CPSR

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Novel mechanistic concepts of the neurobiology of depression and bipolar disorder are evolving based on recent pre-clinical and clinical studies. Ongoing research could lead not only to a breakthrough in identifying the causative factors associated with mood disorders but also to the development of novel therapeutic interventions. One such recent breakthrough concerns the observed abnormalities in the two major signal transduction mechanisms most implicated in mood disorders: adenylyl-cyclase cyclic adenosine monophosphate (AC cAMP) and phosphoinositide (PI) hydrolysis. Among them are abnormalities in GTP binding proteins, phosphorylating enzymes, and substrate molecules observed in peripheral tissues and postmortem brain. More recently, cell survival pathways, such as the extracellular signal-regulated kinase and the Wnt pathways, which also cross-talk with AC-cAMP and PI signaling, have been investigated to elucidate their roles in the pathophysiology of mood disorders. Important consequences of the activation of these diverse signaling pathways are a modulation in the activation of transcription factors and, ultimately, in the regulation of gene expression. Particular attention is being paid to the roles of the transcription factor cAMP-response element binding protein and its target gene, brain-derived neurotrophic factor. Moreover, newer technologies, including complementary DNA microarray analysis, are revealing novel genes relevant to mood disorders. This critical overview presents our own and other groups' findings on various aspects of these signal transduction mechanisms, and on the regulation of gene expression, relevant to the pathophysiology of mood disorders.

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“…Patients with major depression (Ebstein et al 1988) and panic disorder (Maddock et al 1993) exhibit a reduced cyclic AMP response to -adrenergic receptor stimulation of lymphocytes. Patients with bipolar affective disorder showed an increase in Gs protein levels and forskolinstimulated cyclic AMP formation in the cortex but not in the hippocampus, cerebellum and hypothalamus (Young et al 1993) and an impaired down-regulation of -adrenergic receptors in human lymphocytes following incubation with isoproterenol (Kay et al 1993). Therefore, in both mood disorders and schizophrenia the cyclic AMP generating system appears to respond differently from the normal population.…”

Section: Introductionmentioning

confidence: 97%

Increased cyclic AMP response to forskolin in Epstein-Barr virus-transformed human B-lymphocytes derived from schizophrenics

et al. 1997

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Phorbol 12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator, elevated basal cyclic AMP levels and enhanced isoproterenol-, prostaglandin E1- (PGE1), forskolin- and cholera toxin-stimulated cyclic AMP accumulation in Epstein-Barr virus (EBV)-transformed human B-lymphocytes. Staurosporine, a PKC inhibitor, significantly antagonized the increase in cyclic AMP accumulation produced by PMA, whereas the inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD), had no effect. Basal levels of cyclic AMP and the accumulation of cyclic AMP produced by PMA, isoproterenol, PGE1, cholera toxin and the combination of these compounds with PMA were not significantly different between schizophrenics and controls. The cyclic AMP response to forskolin in the presence and absence of PMA was significantly greater in EBV-transformed human B-lymphocytes from schizophrenics. These results suggest that activation of adenylyl cyclase by forskolin is elevated in EBV-transformed B-lymphocytes derived from schizophrenics and that this elevation is further enhanced through a PKC-dependent phosphorylation mechanism.

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The lymphoblast β-adrenergic receptor in bipolar depressed patients: characterization and down-regulation

Cited by 17 publications

References 32 publications

Adenylyl cyclase-cyclicAMP signaling in mood disorders: Role of the crucial phosphorylating enzyme protein kinase A

Adenylyl cyclase-cyclicAMP signaling in mood disorders: Role of the crucial phosphorylating enzyme protein kinase A

The Concept of Dysregulated Signal Transduction and Gene Expression in the Pathophysiology of Mood Disorders

Increased cyclic AMP response to forskolin in Epstein-Barr virus-transformed human B-lymphocytes derived from schizophrenics

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