Multiple α₂‐Noradrenergic Receptor Sites in Rat Brain: Selective Regulation of High‐Affinity [³H] Clonidine Binding by Guanine Nucleotides and Divalent Cations

Both kinetic and equilibrium experiments indicate the presence of distinct high‐ and low‐affinity [³H]clonidine binding associated with α₂‐ noradrenergic receptors in rat cerebral cortex membranes. Guanine nucleotides selectively decrease the numbers of high‐affinity [³H]clonidine binding sites, with no influence on the low‐affinity sites. The influence of nucleotides is exerted by GTP, its nonmetabolized analogue, guanyl‐5′‐yl imidodiphosphate, and GDP–but not by GMP, ADP, ATP, and AMP. In contrast, divalent cations increase high‐affinity [³H]clonidine binding‐an effect not evident at low‐affinity sites. Manganese is the most potent of the divalent cations, while magnesium and calcium are less active. Divalent cations and guanine nucleotides appear to elicit interactive rather than simply additive influences upon α₂‐receptors. The inhibitory influence of sodium upon α₂‐receptor binding of [³H]clonidine is exerted to the same extent upon both high‐ and low‐affinity [³H]clonidine binding.