BK evoked a [Ca2+](i) increase in myenteric neurons and glial cells, both of which were potentiated by treatment with IL-1 beta but not TNF alpha. In both cell types, the [Ca2+](i) responses to BK were abolished by D-Arg(0)[Hyp(3), Thi(5), D-TiC7, Oic(8)]-BK (HOE140), a B2R antagonist, but not affected DNA Damage inhibitor by des-Arg(9)-HOE140, a B1R antagonist. After culture with IL-1 beta, however, the B1R antagonist suppressed the BK-induced [Ca2+](i) increase. Only in glial cells did the B1R agonists des-Arg(9)-BK and BK fragment 1-8 evoke a [Ca2+](i)

rise in a dose-dependent manner. Real time RT-PCR and immunocytochemical analyses showed that IL-1 beta treatment increased expression of B1R mRNA in myenteric plexus cells and B1R protein in glial cells, respectively. Either indomethacin or an EP1 receptor antagonist suppressed the increased [Ca2+](i) response to BK invoked by treatment with IL-1 beta. IL-1 beta treatment increased BK-induced PGE(2) release from cultured myenteric plexus cells.

These results suggest that IL-1 beta promotes up-regulation of B1R expression in glial cells, resulting in the potentiation of neural responses to BK through the elevation of PGE(2) released from glial cells.

The alteration of phenotypes of glial cells may be the cause of the changes in neural function in the enteric nervous system in IBD. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Objective: Matrix gamma-carboxyglutamate (Gla) protein (MGP) is a vitamin K-dependent protein and a strong inhibitor Buparlisib Selumetinib chemical structure of vascular calcification. Vitamin K deficiency leads to inactive uncarboxylated MGP (ucMGP), which accumulates at sites of arterial calcification. We hypothesized that as a result of ucMGP deposition around arterial calcification, the circulating fraction of ucMGP is decreased. Here we report on the development of an ucMGP assay and the potential diagnostic utility of monitoring serum ucMGP levels. Methods and Results: An ELISA-based

assay was developed with which circulating ucMGP can be determined. Serum ucMGP levels were measured in healthy subjects (n = 165) and in four patient populations; patients who underwent angioplasty (n = 30), patients with aortic stenosis (n = 25), hemodialysis patients (n = 52), and calciphylaxis patients (n = 10). All four patient populations had significantly lower ucMGP levels. In angioplasty patients and in those with aortic stenosis, some overlap was observed with the control population. However, in the hemodialysis and calciphylaxis populations, virtually all subjects had ucMGP levels below the normal adult range. Conclusion: Serum ucMGP may be used as a biomarker to identify those at risk for developing vascular calcification. This assay may become an important tool in the diagnosis of cardiovascular calcification. Copyright (C) 2008 S. Karger AG, Basel.