Proton-sensing G-protein-coupled receptors

Blood pH is maintained in a narrow range around pH 7.4 mainly through regulation of respiration and renal acid extrusion. The molecular mechanisms involved in pH homeostasis are not completely understood. Here we show that ovarian cancer G-protein-coupled receptor 1 (OGR1), previously described as a receptor for sphingosylphosphorylcholine, acts as a proton-sensing receptor stimulating inositol phosphate formation. The receptor is inactive at pH 7.8, and fully activated at pH 6.8-site-directed mutagenesis shows that histidines at the extracellular surface are involved in pH sensing. We find that GPR4, a close relative of OGR1, also responds to pH changes, but elicits cyclic AMP formation. It is known that the skeleton participates in pH homeostasis as a buffering organ, and that osteoblasts respond to pH changes in the physiological range, but the pH-sensing mechanism operating in these cells was hitherto not known. We detect expression of OGR1 in osteosarcoma cells and primary human osteoblast precursors, and show that these cells exhibit strong pH-dependent inositol phosphate formation. Immunohistochemistry on rat tissue sections confirms the presence of OGR1 in osteoblasts and osteocytes. We propose that OGR1 and GPR4 are proton-sensing receptors involved in pH homeostasis.     

Evidence of two temperate episodes in late Pleistocene deposits at Marsworth, UK

In the British Quaternary, two post-Cromerian interglacials, the Hoxnian and the Ipswichian, are recognized. Evidence of additional interglacials in this interval is widely accepted in the oceanic record of Quaternary events, and the possibility that at least one additional interglacial of this age is represented in Britain has been discussed. However, in the absence of datable interglacial deposits which are seen to overlie one another, the issue has remained controversial. We describe here deposits at Marsworth, UK (Fig. 1) where there is evidence of two temperate episodes, and of intervening periglacial conditions. Stratigraphical superposition is established beyond any reasonable doubt. The later deposit relates to the temperate woodland stage of the Ipswichian Interglacial. Dating of the earlier temperate material by the 230Th/234U disequilibrium method indicates an interglacial episode not previously established in the British Quaternary.     

Glycine methoxyamide,acyclic analog of cycloserine

Zusammenfassung Methoxy-glycinamid, ein offenkettiges Isomeres von Cycloserin, wurde hergestellt. Seine physikalischen Eigenschaften sind von denjenigen des Cycloserins stark verschieden. Es besitzt keine antibiotische Eigenschaft mehr.