First Experimental Evidence of Dopamine Interactionswith Negatively Charged Model Biomembranes

摘要

Dopamine is essential for receptor-related signal transduction in mammalian central and peripheral nervous systems. Weak interactions between the neurotransmitter and neuronal membranes have been suggested to modulate synaptic transmission; however, binding forces between dopamine and neuronal membranes have not yet been quantitatively described. Herein, for the first time, we have explained the nature of dopamine interactions with model lipid membranes assembled from neutral 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG), and the mixture of these two lipids using isothermal titration calorimetry and differential scanning calorimetry. Dopamine binding to anionic membranes is a thermodynamically favored process with negative enthalpy and positive entropy, quantitatively described by the mole ratio partition coefficient, K. K increases with membrane charge to reach its maximal value, 705.4 ± 60.4 M^–1, for membrane composed from pure DMPG. The contribution of hydrophobic effects to the binding process is expressed by the intrinsic partition coefficient, K⁰. Thevalue of K⁰ = 74.7 ± 6.4 M^–1 for dopamine/DMPG interactions clearly indicates that hydrophobiceffects are 10 times weaker than electrostatic forces in this system.The presence of dopamine decreases the main transition temperatureof DMPG, but no similar effect has been observed for DMPC. Basingon these results, we propose a simple electrostatic model of dopamineinteractions with anionic membranes with the hydrophobic contributionexpressed by K⁰. We suggest that dopamineinteracts superficially with phospholipid membranes without penetratinginto the bilayer hydrocarbon core. The model is physiologically important,since neuronal membranes contain a large (even 20%) fraction of anioniclipids.