6 research outputs found
Binding of Serotonin to Lipid Membranes
Serotonin (5-hydroxytryptamine, 5-HT) is a prevalent
neurotransmitter
throughout the animal kingdom. It exerts its effect through the specific
binding to the serotonin receptor, but recent research has suggested
that neural transmission may also be affected by its nonspecific interactions
with the lipid matrix of the synaptic membrane. However, membrane–5-HT
interactions remain controversial and superficially investigated.
Fundamental knowledge of this interaction appears vital in discussions
of putative roles of 5-HT, and we have addressed this by thermodynamic
measurements and molecular dynamics (MD) simulations. 5-HT was found
to interact strongly with lipid bilayers (partitioning coefficient
∼1200 in mole fraction units), and this is highly unusual for
a hydrophilic solute like 5-HT which has a bulk, oil–water
partitioning coefficient well below unity. It follows that membrane
affinity must rely on specific interactions, and the MD simulations
identified the salt-bridge between the primary amine of 5-HT and the
lipid phosphate group as the most important interaction. This interaction
anchored cationic 5-HT in the membrane interface with the aromatic
ring system pointing inward and a prevailing residence between the
phosphate and the carbonyl groups of the lipid. The unprotonated form
of 5-HT shows the opposite orientation, with the primary amine pointing
toward the membrane core. Partitioning of 5-HT was found to decrease
lipid chain order. These distinctive interactions of 5-HT and model
membranes could be related to nonspecific effects of this neurotransmitter