Down-Regulation of GABAA Receptor via Promiscuity with the Vasoactive Peptide Urotensin II Receptor. Potential Involvement in Astrocyte Plasticity

GABAA receptor (GABAAR) expression level is inversely correlated with the proliferation rate of astrocytes after stroke or during malignancy of astrocytoma, leading to the hypothesis that GABAAR expression/activation may work as a cell proliferation repressor. A number of vasoactive peptides exhibit the potential to modulate astrocyte proliferation, and the question whether these mechanisms may imply alteration in GABAAR-mediated functions and/or plasma membrane densities is open. The peptide urotensin II (UII) activates a G protein-coupled receptor named UT, and mediates potent vasoconstriction or vasodilation in mammalian vasculature. We have previously demonstrated that UII activates a PLC/PIPs/Ca2+ transduction pathway, via both Gq and Gi/o proteins and stimulates astrocyte proliferation in culture. It was also shown that UT/Gq/IP3 coupling is regulated by the GABAAR in rat cultured astrocytes. Here we report that UT and GABAAR are co-expressed in cerebellar glial cells from rat brain slices, in human native astrocytes and in glioma cell line, and that UII inhibited the GABAergic activity in rat cultured astrocytes. In CHO cell line co-expressing human UT and combinations of GABAAR subunits, UII markedly depressed the GABA current (β3γ2>α2β3γ2>α2β1γ2). This effect, characterized by a fast short-term inhibition followed by drastic and irreversible run-down, is not relayed by G proteins. The run-down partially involves Ca2+ and phosphorylation processes, requires dynamin, and results from GABAAR internalization. Thus, activation of the vasoactive G protein-coupled receptor UT triggers functional inhibition and endocytosis of GABAAR in CHO and human astrocytes, via its receptor C-terminus. This UII-induced disappearance of the repressor activity of GABAAR, may play a key role in the initiation of astrocyte proliferation

The Hypothalamic–Pituitary–Adrenal Axis and Anesthetics

International audienceThe hypothalamic–pituitary–adrenal (HPA) axis is essential for human adaptation to stress. However, many anesthetic agents may interfere with the activity of this axis. Although etomidate is known for its suppressive effect on HPA axis function, in vitro evidence suggests that many other drugs used in anesthesia care may also interfere with HPA activity. In this review, we discuss the mechanisms by which all HPA axis activity may be altered during anesthesia and critical care and focus on the impact of hypnotic and analgesic drugs

Accidental Puncture of the Pulmonary Artery during a Subclavian Central Venous Catheterization

The complications associated with central venous catheterization are common and well known. Common malplacement locations have been described in the literature. We report the case of a direct puncture of the pulmonary artery during a subclavian central venous catheterization

Mobile phone text messaging reminder decreases the rate of nonattendance at a preoperative anaesthesia clinic

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