First Experimental Evidence of Dopamine Interactions
with Negatively Charged Model Biomembranes
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Abstract
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-<i>sn</i>-glycero-3-phosphocholine
(DMPC), negatively charged 1,2-dimyristoyl-<i>sn</i>-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, <i>K. K</i> increases with
membrane charge to reach its maximal value, 705.4 ± 60.4 M<sup>–1</sup>, for membrane composed from pure DMPG. The contribution
of hydrophobic effects to the binding process is expressed by the
intrinsic partition coefficient, <i>K</i><sup>0</sup>. The
value of <i>K</i><sup>0</sup> = 74.7 ± 6.4 M<sup>–1</sup> for dopamine/DMPG interactions clearly indicates that hydrophobic
effects are 10 times weaker than electrostatic forces in this system.
The presence of dopamine decreases the main transition temperature
of DMPG, but no similar effect has been observed for DMPC. Basing
on these results, we propose a simple electrostatic model of dopamine
interactions with anionic membranes with the hydrophobic contribution
expressed by <i>K</i><sup>0</sup>. We suggest that dopamine
interacts superficially with phospholipid membranes without penetrating
into the bilayer hydrocarbon core. The model is physiologically important,
since neuronal membranes contain a large (even 20%) fraction of anionic
lipids