• Renlong Zhou, Jose Manuel Perez-Aguilar, Qingcheng Meng, Jeffery G Saven, and Renyu Liu.
• Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, 19104, USA.
• Anesth. Analg.. 2012 Jan 1;114(1):122-8.

BackgroundHuman serum albumin (HSA) is an important carrier for opioids. However, the locations of the binding sites remain unclear. In the present study, we have characterized opioid-HSA interactions using multiple biochemical and biophysical techniques to reveal: (a) the location of the binding site(s); (b) whether naloxone shares the binding site with morphine; and (c) whether opioid agonists share their binding site(s) with general anesthetics.MethodsElution chromatography to determine the global interactions and tryptophan intrinsic fluorescence to determine the localized interactions of opioids with HSA were used. Competition studies using isothermal titration calorimetry were used to determine the overlap of binding site(s) among opioid agonists, antagonists, and general anesthetics. An automatic docking calculation was used to predict the possible binding sites and to assess findings of the solution studies.ResultsFor elution chromatography with immobilized HSA, the retention times of naloxone, morphine, and fentanyl were prolonged but shorter than that of propofol. The inhibition of tryptophan fluorescence by naloxone was not affected by morphine or fentanyl. The calorimetric heat profiles of propofol and halothane interaction with HSA were changed significantly, but not equally by morphine, naloxone, or fentanyl. Consistent with direct binding studies, docking results demonstrated that opioids share sites with general anesthetics; a distinct binding site for naloxone was revealed near the sole tryptophan in HSA that is not shared with morphine.ConclusionsThe interaction of opioids with HSA is weak in comparison with propofol. Naloxone has a distinct binding site in HSA not shared with opioid agonists. Opioids share binding sites with general anesthetics in HSA.

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