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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Evidence for the existence of two forms of alpha 2A-adrenoceptors in the rat.

The alpha 2A-adrenoceptors in rat spleen, kidney, spinal cord and cerebral cortex were studied using [3H]-RX821002 radioligand binding. In the spleen, spinal cord and cerebral cortex, the ligand bound to saturable sites with a Kd of about 1 nmol/l and capacities of 134, 240 and 290 fmol/mg protein, respectively. Computer modelling competition curves for 39 drugs, including those for alpha 2A-, alpha 2B- or alpha 2C-adrenoceptor selective drugs, indicated that the sites labelled by [3H]-RX821002 in the spleen consisted of a single population of alpha 2A-adrenoceptors. However, the competition curves for guanoxabenz were definitely biphasic and resolved into two site fits, indicating that guanoxabenz was binding to both high affinity (Kd = 35 nmol/l) and low affinity (Kd = 8900 nmol/l) alpha 2A-adrenoceptor sites in the proportions 57% and 43%, respectively. The KdS for a number of alpha 2-adrenoceptor subtype selective drugs, measured in competition with [3H]-RX821002 in cerebral cortex and spinal cord, were highly correlated with those obtained in the spleen indicating their alpha 2A-adrenoceptor nature. However, by contrast to the results with the spleen, the guanoxabenz competition curves for the spinal cord and cerebral cortex were monophasic and resolved only into one site fits, the Kd of guanoxabenz being about 4000 nmol/l for both tissues. Drug KdS for kidney alpha 2A-adrenoceptors were also determined using [3H]-RX821002. For nearly all drugs tested, the KdS were highly correlated with those found for the alpha 2A-adrenoceptors in the other rat tissues.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


  1. Evidence for the existence of two forms of alpha 2A-adrenoceptors in the rat. Uhlén, S., Xia, Y., Chhajlani, V., Lien, E.J., Wikberg, J.E. Naunyn Schmiedebergs Arch. Pharmacol. (1993) [Pubmed]
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