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Publications Research Projects The oxytocin receptor and its dependence on cholesterol Oxytocin is a neurohypophyseal nonapeptide that can induce several physiological (peripheral and central) responses. Among the best-known peripheral effects of oxytocin are the contraction of smooth muscles in the myometrium (labor inducing) and myoepithelial cells of the mammary gland (lactation). One special property of the oxytocin receptor refers to its dependence on cholesterol. The high-affinity state of the oxytocin receptor requires the presence of a high cholesterol environment. Cholesterol also has a stabilizing function for the receptor. Many findings suggest that one or more cholesterol molecules directly interact with the receptor. Synthesis of fluorescent cholesterol analogues Cholesterol is a multifunctional lipid and main structural component of the plasma membrane of higher eucaryotic cells. The intracellular cholesterol concentration is tightly regulated by feedback controls. However, despite much efforts, the transport pathways of cholesterol in the cell are ill-defined. To study the cellular trafficking of cholesterol, we have synthesized novel fluorescent cholesterol analogues. Among these analogues 6-Dansylcholestanol (DChol) was found to be the most appropriate. In CHO cells, we could demonstrate that DChol is esterified with the same kinetics as compared with tritiated cholesterol (Wiegand et al., 2003). DChol applied in form of water soluble cyclodextrin inclusion complexes translocated from the plasma membrane to the endoplasmic reticulum (ER)/Golgi in an energy-independent manner. The kinetics of this transport process was cell-type dependent. Finally, DChol is esterified by acyl-CoA cholesterol acyltransferase (ACAT), an enzyme localized in the ER, and is stored in lipid droplets. The in vivo dynamics of the cholesterol transport and the biogenesis of lipid droplets are studied. Technical assistant: Coworkers: |
