125I]-HEAT:fifty percent of the ligand can bind to the alpha1-adrenoceptors with extremely high affinity
Naunyn-Schmiedeberg's Archives of Pharmacology
H Glossmann, F Lübbecke
-HEAT, 125iodo-2-[Beta-(4-hydroxyphenyl)-ethyl-aminomethyl]tetralone, is a novel alpha1-adrenoceptor ligand which labels alpha1-adrenoceptors in peripheral tissues as well as in the central nervous system. Using the technique of ligand saturation by receptors, we find that only 50% of the 125I-labeled HEAT molecules bind with high affinity to receptors from a variety of tissues. This was observed with partially purified rat brain membranes and highly purified rat liver plasma membranes in the absence or presence of sodium ion (as NaCl, 150 mM) which stimulated 125I-HEAT binding, by increasing the affinity. If the bindability of [125I]-HEAT is taken into account, KD values as low as 7-8 pM (at 30 degrees C) are found in equilibrium binding experiments and optimally stimulating concentrations of sodium ion. The limited high affinity binding of [125I]-HEAT could not be explained by radiochemical impurities. Instead, we suggest that only one enantiomer of the racemic ligand is preferentially bound to the receptors with a KD in the picomolar range. Since the enantiomers are in dynamic equilibrium in solution (via keto-enol tautomerism) [125-I]-HEAT is a unique radioligand which makes it unlikely that the respective isomers can ...Continue Reading
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