Abstract
The binding of agonists and antagonists to Ri adenosine receptors
of synaptosomal membranes from rat and bovine brain was studied.
The effects of guanine nucleotides and temperature were analyzed
with the aid of computerized curve fitting. Evidence is presented
for two different states of the receptor: one of high and one of
low affinity for agonists. Antagonists bind to both states with the
same affinity. The two states are characterized by saturation, competition,
and kinetic experiments with very similar results. Guanine nucleotides
cause transition of the high- to the low-affinity state. The ratio
of the KD values for the two affinity states is 90-150 in rat brain
but only 10 in bovine brain. The proportions of the two affinity
states are the same for all agonists tested; in the absence of exogenous
guanine nucleotides, 75% of the total receptor population is in the
high-affinity state, whereas in the presence of guanine nucleotides
only 5% remain in the high-affinity state. Binding of antagonists
to the receptor is enthalpy-driven whereas binding of the agonist
(-)-N6-phenylisopropyladenosine to the high-affinity state of the
receptor is entropy-driven. Binding of the agonist to the low-affinity
state is enthalpy-driven and thus similar to the binding of antagonists.
Our data indicate that guanine nucleotides convert the Ri adenosine
receptor from a high- to a low-agonist affinity state and that agonist
binding shows thermodynamic differences from antagonist binding only
when it is to the high-affinity state of the receptor.
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