Biomedical subjects

A Lymperopoulos

Publications and source records attributed to A Lymperopoulos.

3 recordsLinked to original sources

PubMed2006

Alpha 2-adrenergic receptors decrease DNA replication and cell proliferation and induce neurite outgrowth in transfected rat pheochromocytoma cells.

Alpha 2-adrenergic receptors (alpha(2)-ARs) have a widespread distribution in the central nervous system (CNS) and affect a number of biochemical and behavioral functions, including stimulation of prefrontal cortex (PFC) and cognitive function. In addition to its role as a classical neurotransmitter, norepinephrine (NE) has been recently shown to exert an important influence on the plasticity in areas of the brain where neurogenesis persists in the adult, notably the subgranular zone (SGZ) within the dentate gyrus of the hippocampus and the olfactory bulb (OB). In regulating adult neurogenesis, the noradrenergic system is functionally integrated with chronic stress and depression. Chronic stress, depression, or depletion of NE in vivo suppress, and antidepressant treatments induce hippocampal neurogenesis by down- or upregulating, respectively, cell proliferation. In the present study we show that alpha(2)-AR subtypes promote the differentiation rather than cell proliferation of PC12 cells. It is conceivable that alpha(2)-ARs might contribute neurotrophic actions in vivo synergistically or in permutation with other neurotrophic factors.

Adrenergic alpha-Agonists↗

PubMed2004

Pharmacogenomics of adrenoceptors.

Adrenoceptors (ARs) consist of nine subtypes (alpha(1A)-, alpha(1B)-, alpha(1D)-, beta(1)-, beta(2)-, beta(3)-, alpha(2A)-, alpha(2B)- and alpha(2C)-AR), which are involved in a wide spectrum of physiological functions and are the site of action for a considerable percentage of currently prescribed therapeutics. With the exception of alpha(1D), all AR subtypes are polymorphic with genetic variations in the coding and non-coding regions. This review discusses the biochemical consequences of these genetic variations and their impact in receptor function, disease pathophysiology, and drug response. Pharmacogenomic principles that have been discovered are also discussed.

Animals↗

PubMed2000

Transcriptional down-regulation of the human alpha2C-adrenergic receptor by cAMP.

The heterologous regulation of the alpha2C-adrenergic receptor (alpha2C-AR) was investigated in the HepG2 cell line. Binding of [(3)H]MK912 (alpha2-antagonist) to membranes from cells submitted to various treatments showed that exposure to insulin, phorbol 12-myristate 13-acetate, or dexamethasone did not affect receptor density. On the other hand, treatment with forskolin resulted in a large reduction of alpha2C-AR number. The effect of forskolin was mimicked by 8-br-cAMP and was abolished by the protein kinase A inhibitor, H89. The action of cAMP was slow (t(1/2) = 23 h), dose-dependent, and additive to the receptor down-regulation elicited by the alpha2-agonist, UK14304. Furthermore, the diminution of receptor was not caused by an increased rate of its degradation but resulted from a decrease in the steady state amounts of alpha2C4-mRNA. As assessed by experiments in the presence of actinomycin D, the stability of alpha2C4-mRNA was not affected by 8-br-cAMP or forskolin. By contrast, the activity of a luciferase construct containing the entire promoter region of the alpha2C4 gene (1.9 kilobase pairs) was inhibited, indicating that the primary mechanism of action of the two compounds is at the transcriptional level. Deletions in the 5'-end of this construct showed that the elements responsible for cAMP responsiveness lie within a 242-base-pair fragment of the gene promoter (nucleotides -236/+6 relative to transcription start). Band-shift experiments indicated that nuclear factors bind to this region in a cAMP-dependent manner. The determination of the actual cis- and trans-acting elements involved will be the object of future investigation, but the present study provides evidence for transcriptional regulation of human alpha2C-AR by cAMP.

8-Bromo Cyclic Adenosine Monophosphate↗