Regional Variations in α₁‐Adrenergic Receptor Subtypes in Rat Brain

Abstract

alpha 1-Adrenergic receptor subtypes were differentiated by their affinities for the competitive antagonist WB 4101 and their sensitivities to inactivation by chlorethylclonidine (CEC) in eight rat brain regions. WB 4101 showed low Hill coefficients for inhibition of specific 125I-[2-beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125IBE) binding in all regions. Nonlinear regression analysis showed that there were two binding sites with different affinities for WB 4101 in each region. The proportions of these sites varied among regions, although the affinity of WB 4101 for each site remained constant. Thalamus and cerebral cortex had the highest proportion of low-affinity sites, whereas hippocampus and pons-medulla had the highest proportion of high-affinity sites. Pretreatment with CEC in hypotonic buffer significantly reduced the density of 125IBE binding sites in all brain regions. Cerebral cortex and cerebellum had the highest proportion of CEC-sensitive sites, whereas hippocampus and spinal cord had the highest proportion of CEC-insensitive sites. There was a significant correlation between the proportion of binding sites with a low affinity for WB 4101 and those sensitive to inactivation by CEC.

α1A-Adrenergic Receptors Are Functionally Expressed by a Subpopulation of Cornu Ammonis 1 Interneurons in Rat Hippocampus

“…Previous in situ studies also demonstrate ␣ 1B AR mRNA in CA1 (Pieribone et al, 1994;Day et al, 1997), although these studies often report ␣ 1A AR expression in the hippocampus at a greater density. The predominance of ␣ 1A AR subtype expression in the hippocampus is supported by binding studies (Wilson and Minneman, 1989) and more specifically in CA1 hippocampus by enhanced green fluorescent protein-tagged ␣ 1 AR localization experiments (Papay et al, 2006). One could speculate that both ␣ 1A and ␣ 1B AR subtypes are transcribed in CA1, with only the ␣ 1A AR translating into a functional protein.…”

Distribution of ?1A adrenergic receptor m RNA in the rat brain visualized by in situ hybridization

“…While anatomical resolution by pharmacologic differentiation has been only coarse at best, it has generally been suggested that the ␣ 1A receptor binding site was most exclusively represented in hippocampus, while the ␣ 1B receptor predominated in thalamus, with both binding sites present in cortex (Wilson and Minneman, 1989). More recently, with molecular cloning of cDNAs coding for the ␣ 1 receptors, it has become clear that there are at least three ␣ 1 receptor subtypes for which mRNA are expressed in brain and other tissues.…”

α1-Adrenergic receptor subtypes: non-identical triplets with different dancing partners?

“…Although the density of a 1 -ARs in the CNS is among the highest of any tissue in the body (Wilson and Minneman, 1989), it has been difficult to determine their functional role. To a large extent, this is due to the inability of many a 1 -AR agonists and antagonists to cross the blood-brain barrier (Pupo and Minneman, 2001).…”