Solubilization of brain alpha-2 adrenoceptor with a zwitterionic detergent: preservation of agonist binding and its sensitivity to GTP.

Alpha-2 adrenergic receptors were solubilized from calf cerebral cortex using the zwitterionic detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate. The soluble extract retained the ability to bind the partial alpha 2 - adrenergic agonist [3H] p-aminoclonidine. This binding was of high affinity (KD = 1.5 +/- 0.3 nM) saturable (Bmax = 150 +/- 24 fmol/mg) and reversible. The orders of potencies of alpha-adrenergic drugs and nucleotides, for inhibition of binding, paralleled those previously observed on membrane bound alpha 2-adrenoceptors. Furthermore the very rapid decrease of [3H] p-amino-clonidine binding induced by GTP suggest that the guanyl nucleotide effect is due to an allosteric mechanism. These results indicate that in the soluble extract the interaction between the alpha 2-adrenoceptor and the GTP-binding regulator protein is preserved thus providing an interesting model to study the molecular structure of this system.