Magnesium reduces affinities of antagonists at rat cortex alpha 2-adrenergic receptors labeled with 3H-clonidine: evidence for heterogeneity of alpha 2-receptor conformations with respect to antagonists.

3H-clonidine labeled two binding sites in rat cortex membranes with apparent KD values of about 1.0 and 5.9 nM. These sites appeared analogous to "super-high" (SH) and "high" (H) affinity states of the alpha 2-receptor described in human platelets. 10 mM magnesium increased the number of SH receptors by 30% whereas 100 microM GTP reduced SH receptor number by 45% with no significant change in the KD of 3H-clonidine at alpha 2 (SH) sites. IN drug competition studies using 1.0 nM 3H-clonidine, 100 microM GTP reduced the affinity of clonidine and increased the affinity of yohimbine, whereas 10 mM magnesium increased the affinity of clonidine and reduced the affinity of yohimbine. The effect of magnesium on the affinity of several antagonists at cortex 3H-clonidine sites ranged from none (phentolamine) to a 6-fold reduction (piperoxan). These data indicate that different states of the alpha 2-receptor exhibit different affinities for some antagonists.