Abstract
The binding of agonists and antagonists to alpha 2-adrenergic receptors
of human platelets was studied. The receptors showed homogeneous
affinities for antagonists but two affinity states for the agonist
(-)-epinephrine, which were modulated by guanine nucleotides. Van't
Hoff plots of antagonist binding had a break point at about 18 degrees
and considerable diversity between 18 degrees and 0 degree. Agonist
binding to both affinity states showed a similar break point; agonist
binding to the high affinity state was characterized by a large entropy
component compared to the low affinity state. This entropy component
was reduced at higher concentrations of sodium, indicating that it
may be due to liberation of sodium ions. Measurements of the fluorescence
of 1-anilin-8-naphthalenesulfonate showed thermotropic phase transitions
of the platelet membranes at about 17 degrees. The transition temperature
was decreased to about 12 degrees by addition of 10 mM octanoic acid.
Octanoic acid also shifted the break points of the van't Hoff plot
of antagonist and low affinity agonist binding from 18 degrees to
12 degrees. High affinity agonist binding, however, remained unchanged.
It is concluded that agonist-specific thermodynamic characteristics
of ligand binding to alpha 2-receptors of human platelets can only
be investigated by regarding differences between high and low affinity
agonist binding. These differences include an entropy increase upon
ligand binding, which is in part due to enhanced liberation of sodium
ions, and a loss of sensitivity to fluidity changes in the outer
layer of the plasma membrane.
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