Leukemia (2009) 23, 1080-1086; doi: 10.1038/leu.2009.7; published online 12 February 2009″
“Due to entangled results concerning K(v)11 subunit distribution in the gastrointestinal wall, we aimed to unravel the expression of the delayed rectifier potassium subunits
K(v)1.1 and K(v)1.2 in the murine ileum. Presence and distribution of both subunits were determined in cryosections and whole-mount Cobimetinib purchase preparations of the ileum of three different murine strains by indirect immunofluorescence, and analysed by conventional fluorescence and confocal microscopy. Distribution of both subunits was similar in the ileum of the three strains. K(v)1.1 immunoreactivity (IR) was found in some S100-expressing enteroglial cells (EGC) located at the periphery of myenteric ganglia, in S100-positive EGC along interganglionic, intramuscular and vascular nerve fibres, and in S100-positive EGC of the submucous plexus. K(v)1.1 IR was also observed in some GFAP-expressing EGC at the periphery of myenteric ganglia, BIBF 1120 and in GFAP-positive EGC of submucous ganglia. K(v)1.2 IR was detected in some intramuscular S100-positive EGC, in almost
all submucous S100-expressing EGC, and in a few GFAP-expressing EGC. K(v)1.2 IR was also expressed in a majority of enteric neurons. Coding of these neurons showed that all cholinergic and most nitrergic neurons express K(v)1.2. In conclusion, the results showed that K(v)1.1 and K(v)1.2 were predominantly expressed in distinct EGC phenotypes. K(v)1.2 was also observed in distinct neuron subpopulations. Our results support the active role of EGC with distinct phenotypes in intestinal functions, which is relevant in view of their modulating role on intestinal barrier and inflammatory responses. (C) 2009
Elsevier Ireland Ltd. All rights reserved.”
“Concurrent treatment with methotrexate (MTX) and antiepileptic drugs, such as phenobarbital (PB), reduces the efficacy of MTX chemotherapy in childhood Dimethyl sulfoxide acute lymphoblastic leukemia (ALL). This can result from defective Reduced folate carrier (Rfc1)-dependent cellular uptake of MTX. Indeed, we have shown that functional Rfc1 activity is significantly reduced by clinically relevant concentrations of the anticonvulsant drugs PB or carbamazepine in an adequate in vitro model. As PB is known to regulate carrier-associated transport by the nuclear receptor constitutive androstane receptor (CAR), we investigated the involvement of the CAR signaling cascade and the mode of PB-induced downregulation of Rfc1 activity. CAR activation by PB or the CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene resulted in translocation of Ca(2+)-dependent protein kinase C alpha (cPKC alpha) to the plasma membrane related to significantly elevated PKC activities. In contrast, subcellular localization of Ca(2+)-independent PKC delta was only marginally altered.