and the American Pharmacists Association J Pharm Sci 99:325-335, 2010″
“beta(3)-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but Tariquidar in vitro susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced beta(3)-adrenoceptor desensitization in

HEK cells. Cells were treated with isoprenaline or forskolin, and following wash-out, cyclic adenosine monophosphate (cAMP) accumulation in response to freshly added agonist was quantified. Receptor and G protein expression were quantified by radioligand binding and immunoblot experiments, respectively. Treatment with isoprenaline induced a concentration- AZD2171 chemical structure and time-dependent desensitization of cAMP accumulation in response to freshly added isoprenaline. This functional desensitization primarily consisted of reduced maximum responses with little change of agonist potency. Maximum desensitization was achieved by pre-treatment with 10 mu M isoprenaline for

24 h. It was not accompanied by changes in beta(3)-adrenoceptor density as assessed in saturation radioligand-binding studies. The desensitization was associated with a small reduction in immunoreactivity for alpha-subunits for G(s) and G(i1), whereas that for G(i2), G(i3), and G(q/11) was not significantly altered. In cells treated with pertussis toxin, isoprenaline-induced cAMP accumulation as well as desensitization by isoprenaline pre-treatment remained unchanged. Isoprenaline GSK1904529A concentration pre-treatment also reduced forskolin-induced cAMP accumulation; conversely, pre-treatment with forskolin caused a similar desensitization

of isoprenaline-induced cAMP accumulation. We conclude that agonist-induced beta(3)-adrenoceptor desensitization in HEK cells does not involve reduced receptor numbers and small, if any, reduction of G(s) expression; changes at the level of adenylyl cyclase function can fully explain this desensitization.”
“Background: Recent technological advances applied to biology such as yeast-two-hybrid, phage display and mass spectrometry have enabled us to create a detailed map of protein interaction networks. These interaction networks represent a rich, yet noisy, source of data that could be used to extract meaningful information, such as protein complexes. Several interaction network weighting schemes have been proposed so far in the literature in order to eliminate the noise inherent in interactome data. In this paper, we propose a novel weighting scheme and apply it to the S. cerevisiae interactome. Complex prediction rates are improved by up to 39%, depending on the clustering algorithm applied.\n\nResults: We adopt a two step procedure. During the first step, by applying both novel and well established protein-protein interaction (PPI) weighting methods, weights are introduced to the original interactome graph based on the confidence level that a given interaction is a true-positive one.