3H]Para-amino-clonidine: a novel ligand which binds with high affinity to alpha-adrenergic receptors.

Para-amino-clonidine (PAC) is an α-adrenergic agonist with extraordinarily high potency in some peripheral tissues. We have demonstrated the labeling of α-adrenergic binding sites in central and peripheral tissues with ³H]PAC and compared properties of this binding to those of ³H]clonidine. ³H]PAC binds saturably with a dissociation constant (K_D) of about 0.9 nM to rat cerebral cortex membranes. It has about 2–3 times the affinity of ³H]clonidine for α-receptor binding sites. The greater affinity is attributable mainly to a slower dissociation of ³H]PAC than ³H]clonidine from binding sites. The relative and absolute potencies of various adrenergic agonists and antagonists in competing for ³H]PAC and ³H]clonidine binding are essentially the same. ³H]PAC can also be utilized to label α-adrenergic binding sites in the kidney and spleen where the relative potencies of PAC and clonidine are the same as in the brain.