The hydrophobic tryptic core of the porcine alpha 2-adrenergic receptor retains allosteric modulation of binding by Na+, H+, and 5-amino-substituted amiloride analogs.

Extensive trypsinization of the purified alpha 2-adrenergic receptor and repurification by wheat germ agglutinin-agarose chromatography yields an adrenergic ligand-binding hydrophobic core of the receptor. Allosteric modulation of adrenergic ligand binding by Na+, H+, and 5-amino-substituted analogs of amiloride is quantitatively retained in this core, as assessed by the ability of these agents to accelerate the rate of [3H] yohimbine dissociation from the adrenergic ligand-binding site. These findings refine our understanding of where within the alpha 2-adrenergic receptor structure these allosteric agents bind and, for the effects of Na+ and H+, allow certain predictions to be made as to which carboxylic acid side chains are probable candidates for participation in a monovalent cation-binding pocket within the hydrophobic tryptic core of the receptor.