Comparison of the abilities of GDP and GTP gamma S to modulate high affinity agonist binding to 5-HT1A receptors indicated that both nucleotides were

almost 10-fold less potent in the presence of MnCl2 compared to MgCl2. This means that by inhibiting guanosine nucleotide binding to G proteins in complex with 5-HT1A receptors, Mn2+ acts as an enhancer for agonist binding and signal transduction. As the influence of Mn2+ resembles the hypersensitivity of dopaminergic system in Parkinsonial models, it can be proposed that at least some symptoms of manganism are connected with a change of signal transduction complex caused by manganese-nucleotide complexes. (C) 2010 Elsevier Inc. All rights reserved.”
“It has been postulated that a flow-dependent (and hence spatially varying)

low density lipoprotein (LDL) concentration polarisation layer forms on the luminal surface of the vascular endothelium. AZD2281 chemical structure Such a layer has the potential to cause heterogeneity in the distribution of atherosclerotic CHIR-99021 lesions by spatially modulating the rate of LDL transport into the arterial wall. Theoretical analysis suggests that a transmural water flux which is spatially heterogeneous at the cellular scale can act to enhance LDL concentration polarisation in a shear dependent fashion. However, such an effect is only observed if a relevant Peclet number (i.e. the ratio of LDL convection to LDL diffusion) is of order unity or greater. Based on the diffusivity of LDL in blood plasma, such a Peclet number is found to be far less this website than unity, implying that the aforementioned enhancement and shear dependence will not occur. However, this conclusion ignores the existence of the endothelial glycocalyx layer (EGL), which may inhibit the diffusion of LDL near the luminal surface of the endothelium, and hence raise any Peclet number associated with the transport of LDL. The present

study numerically investigates the effect of the EGL, as well as a heterogeneous transmural water flux, on arterial LDL concentration polarisation. Particular attention is paid to measures of LDL concentration polarisation thought relevant to the rate of transendothelial LDL transport. It is demonstrated that an EGL is unlikely to cause any additional shear dependence of such measures directly, irrespective of whether or not LDL can penetrate into the EGL. However, it is found that such measures depend significantly on the nature of the interaction between LDL and the EGL (parameterised by the height of the EGL, the depth to which LDL penetrates into the EGL, and the diffusivity of LDL in the EGL). Various processes may regulate the interaction of LDL with the EGL, possibly in a flow dependent and hence spatially non-uniform fashion.