Chronic alcohol feeding potentiates hormone-induced calcium signalling in hepatocytes.

Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined. We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca -mobilizing hormones resulting in a leftward shift in the concentration-response relationship and the transition from oscillatory to more sustained and prolonged Ca increases. Our data demonstrate that alcohol-dependent adaptation in the Ca signalling pathway occurs at the level of hormone-induced inositol 1,4,5 trisphosphate (IP ) production and does not involve changes in the sensitivity of the IP receptor or size of internal Ca stores.

Dynamics of the Ins(1,4,5)P3 receptor during polarization of MDCK cells.

Background Information: The uneven distribution of the Ins(1,4,5)P3R [Ins(1,4,5)P3 receptor] within the ER (endoplasmic reticulum) membrane generates spatially complex Ca2+ signals. The ER is a dynamic network, which allows the rapid diffusion of membrane proteins from one part of the cell to another. However, little is known about the localization and the dynamics of the Ins(1,4,5)P3R in the ER of living cells.

D-myo-inositol-1,4,5-trisphosphate and adenophostin mimics: importance of the spatial orientation of a phosphate group on the biological activity.

Three different routes for the synthesis of heterocyclic analogues of the second messenger D-myo-inositol-1,4,5-trisphosphate (InsP(3)) and the natural adenophostins, starting from allyl D-xyloside are described. The two diastereoisomers at C-2 of new compounds, which we named xylophostins, were obtained. The preliminary biological studies shows that the presence of the adenine residue has a beneficial effect on the affinity for the receptor.