“
“5-HT1A receptors were studied via [H-3]WAY-100635 and [H-3]8-OH-DPAT binding to rat brain cortical membranes. We characterized the effect of zinc (Zn2+) on the binding properties of the 5-HT1A receptor. The allosteric ternary complex model was applied to determine the

dissociation constant (K-A) of Zn2+ and their cooperativity factors (alpha) affecting the dissociation constants (K-D, K-i) of [H-3]WAY-100635, [H-3]8-OH-DPAT, and serotonin (5-HT), the endogenous neurotransmitter. Zn2+ (5 mu M-1 mM) inhibited the binding of agonist/antagonist to 5-HT1A receptors, mostly by decreasing both the ligands’ affinity Defactinib and the maximal number of sites. In [S-35]GTP gamma S binding assays Zn2+ behaved as insourmountable antagonist of 5-HT1A receptors, in agreement with radioligand binding assays. The residues involved in the formation of the inhibitory binding site on the 5-HT1A receptor were assessed by using N-ethyl-maleimide (NEM) or diethylpyrocarbonate (DEPC) which modify preferentially cysteine and histidine residues, respectively. Exposure to both agents did not block the negative allosteric GDC-0994 molecular weight effects of Zn2+ on agonist and antagonist binding. Our findings represent the first quantitative analysis of allosteric binding interactions for 5-HT1A receptors. The physiological significance of Zn2+ modulation of 5-HT1A receptors is unclear, but the colocalization of 5-HT1A receptors

and Zn2+ in the nervous system (e.g. in the hippocampus and cerebral cortex) suggests that Zn2+ released at nerve terminals may modulate signals generated by the 5-HT1A receptors in vivo. Finally, these findings suggest that synaptic Zn2+ may be a factor influencing Galactosylceramidase the effectiveness of therapies that rely on 5-HT1A receptor activity (c) 2008 Elsevier Ltd. All rights reserved.”
“We

investigated the ability of western equine encephalitis virus envelope glycoproteins (WEEV GP) to pseudotype lentiviral vectors. The titers of WEEV GP-pseudotyped human immunodeficiency virus type 1 (HIV) ranged as high as 8.0 X 10(4) IU/ml on permissive cells. Sera from WEEV-infected mice specifically neutralized these pseudotypes; cell transduction was also sensitive to changes in pH. The host range of the pseudotyped particles in vitro was somewhat limited, which is atypical for most alphaviruses. HIV vectors pseudotyped by WEEV GP may be a useful tool for characterizing WEEV cell binding and entry and screening for small-molecule inhibitors.”
“Significant advances have been made in understanding the underlying defects of and developing potential treatments for Fragile X syndrome (FXS), the most common heritable mental retardation. It has been shown that neuronal metabotropic glutamate receptor 5 (mGluR5)-mediated signaling is affected in FX animal models, with consequent alterations in activity-dependent protein translation and synaptic spine functionality.