Guanine nucleotides, divalent cations, and sodium differentially regulate agonist and antagonist binding to adenosine A1 receptors in brain membranes. Guanine nucleotides decrease the binding of the adenosine A1 receptor agonist [3H]N6-cyclohexyladenosine ([3H]CHA) to guinea pig and bovine brain membranes by about 50% at 1-3 μM, while not affecting binding of the antagonist [3H]1,3-diethyl-8-phenylxanthine ([3H]DPX) to A1 receptors in bovine brain. GTP decreases the potency of agonists competing for [3H]DPX binding by 3-6 times, without altering the potency of antagonists. This effect can be used to grade experimental substances along an adenosine agonist-antagonist continuum. The 66% inhibition of [3H]CHA binding by 1 mM EDTA, with no change in [3H]DPX binding, suggests that endogenous divalent cations may regulate adenosine receptor interactions. Removal of endogenous divalent cations by EDTA treatment greatly increases the enhancement of [3H]CHA binding by divalent cations. Specific binding of [3H]CHA to guinea pig brain is increased 150-170% by 0.3-1.0 mM Mn2+, Mg2+, and Ca2+ following EDTA preincubation, secondary to an increase in apparent affinity and receptor number. Sodium ions also selectively regulate the binding of [3H]CHA. Sodium decreases [3H]CHA binding 40%, whereas lithium and potassium are ineffective. Sodium does not affect [3H]DPX binding.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Jan 1 1982|
ASJC Scopus subject areas
- Molecular Medicine