Scatchard analyses of
3H-prazosin binding in rat brain membranes showed biphasic curves, which identified the presence of α
1High- and α
1Low-affinity sites. The α
1High-affinity site was completely inhibited by 0.1 μM phenoxybenzamine. On the other hand,
3H-prazosin binding in rat spleen membranes resulted in linear curves that were identical to the binding curve for the α
1High-affinity site in the brain. The displacement potencies of α
1-adrenergic antagonists were characterized by
3H-prazosin binding to α
1High-affinity sites in the rat spleen and brain and α
1Low-affinity sites in the brain in the presence of 0.1 μM of phenoxybenzamine. The affinities of WB-4101, phenoxybenzamine, phentolamine, chlorpromazine, labetalol and nifedipine for brain α
1High-affinity sites were significantly higher than those in the spleen. The affinities of most ligands for α
1Low-affinity sites were significantly lower than those for both α
1High-affinity sites in the brain and spleen, but chlorethylclonidine was significantly selective for α
1Low-affinity sites, and bunazosin, dibenamine and 5HT had the same affinities for the α
1Low- and both α
1High-affinity sites. These results show that two α
1-adrenoceptor subtypes, α
1High- and α
1Low-affinity, are present in the rat brain and that a different α
1High-subtype, exists in the rat spleen.
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