TAILIEUCHUNG - Báo cáo Y học: A pool of Y2 neuropeptide Y receptors activated by modifiers of membrane sulfhydryl or cholesterol balance

The cloned guinea-pig Y2 neuropeptide Y (NPY) receptors expressed in Chinese hamster ovary (CHO) cells, as well as the Y2 receptors natively expressed in rat forebrain, are distributed in two populations. A smaller population that is readily accessed by agonist peptides on the surface of intact cells constitutes less than 30% of Y2 receptors detected in particulates after cell homogenization. A much larger fraction of cell surface Y2 sites can be activated by sulfhydryl modifiers. A fast and large activation of these masked or cryptic sites could be obtained with membrane-permeating, vicinal cysteine-bridging arsenical phenylarsine oxide. A lower activation is. | Eur. J. Biochem. 269 2315-2322 2002 FEBS 2002 doi PRIORITY PAPER A pool of Y2 neuropeptide Y receptors activated by modifiers of membrane sulfhydryl or cholesterol balance Steven L. Parker1 Michael S. Parker2 Justin K. Kane1 and Magnus M. Berglund3 1 Department of Pharmacology University of Tennessee College of Medicine Memphis TN USA 2 Department of Microbiology and Molecular Cell Sciences University of Memphis TN USA 3Unit of Pharmacology Department of Neuroscience University of Uppsala Sweden The cloned guinea-pig Y2 neuropeptide Y NPY receptors expressed in Chinese hamster ovary CHO cells as well as the Y2 receptors natively expressed in rat forebrain are distributed in two populations. A smaller population that is readily accessed by agonist peptides on the surface of intact cells constitutes less than 30 of Y2 receptors detected in particulates after cell homogenization. A much larger fraction of cell surface Y2 sites can be activated by sulfhydryl modifiers. A fast and large activation of these masked or cryptic sites could be obtained with membrane-permeating vicinal cysteine-bridging arsenical phenylarsine oxide. A lower activation is effected by N-ethylmaleimide an alkyla-tor that slowly penetrates lipid bilayers. The restricted-access alkylator 2- trimethylammonium ethyl methanethiosulfo-nate was not effective in unmasking these sites. Some of the hidden cell surface Y2 sites could be activated by polyene filipin III through complexing of membrane cholesterol. The results are consistent with the presence of a large Y2 reserve in a compartment that can be accessed by alteration of sulfhydryl balance or fluidity of the cell membrane and by treatments that affect the anchoring and aggregation of membrane proteins. Keywords receptor sequestration receptor reserve receptor signaling receptor masking. Synaptic discharge of many neurotransmitters produces concentrations of these receptor agonists that saturate the respective .

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