Cholesterol as stabilizer of the oxytocin receptor.
The function of the oxytocin receptor system is strongly dependent on steroids as demonstrated by several physiological studies. One key element of this dependence on steroids may be the interaction of cholesterol and the oxytocin receptor. In this study, we show that cholesterol stabilizes the solubilized human oxytocin receptor against thermal inactivation and proteolytic degradation. In the absence of additional cholesterol, the soluble receptor inactivates within minutes. Maximal stabilization of the oxytocin receptor requires a continuous supply with cholesterol from a cholesterol-rich environment. A structure-activity analysis of various cholesterol analogues and their effect on the thermal stability of the oxytocin receptor showed that the stabilizing function of cholesterol was highly specific. The structural requirements of a potent stabilizing steroid are very similar to those necessary to support the high-affinity state of the receptor. Moreover, in the presence of cholesterol, the oxytocin receptor is significantly more stable against alterations of pH value (pH 4-12). The results show that cholesterol acts as a general stabilizer of the oxytocin receptor.
Gimpl
Gerald
G
Institute of Biochemistry, Johannes Gutenberg-University of Mainz, Becherweg 30, D-55099, Mainz, Germany. gimpl@mail.uni-mainz.de
Fahrenholz
Falk
F
D002460:Cell Line; D002784:Cholesterol / Q000172:deficiency / Q000494:pharmacology*; D010450:Endopeptidases; D049452:Green Fluorescent Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008164:Luminescent Proteins; D018045:Receptors, Oxytocin / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects*; D012995:Solubility; D013696:Temperature; D014162:Transfection
D008164:Luminescent Proteins; D018045:Receptors, Oxytocin; D049452:Green Fluorescent Proteins; D002784:Cholesterol; D010450:Endopeptidases