Delineation of rat kidney α2A- and α2B-adrenoeeptors with [3H]RX821002 radiollgand binding: computer modelling reveals that guanfacine is an α2A-selective compound

doi:10.1016/0014-2999(91)90299-6

European Journal of Pharmacology

Volume 202, Issue 2, 17 September 1991, Pages 235-243

https://doi.org/10.1016/0014-2999(91)90299-6 Get rights and content

Abstract

We developed a method for the simultaneous determination of drug affinity constants for rat α_2A- and α_2B-adrenoceptor subtypes by using [³H]RX821002 radioligand binding in the kidney. Three competition curves were obtained for each drug: one for the test compound in the absence of ARC 239 (a drug found to have 108-fold higher affinity for α_2B- than for α_2A-adrencceptors), one in the presence of ARC 239, and one for ARC 239. It is possible to determine the K_ds of a tested drug for both α_2A- and α_2B-adrenoceptors by simultaneous computer modelling because of the increased constrain; in the calculations given by the inclusion of ARC 239 into the assay. Using this approach, we found guanfacine and oxymetazoline to be highly α_2A-seIective, The most α_2B-selective were ARC 239, prazosin and corynanthine. A number of other drugs, for example UK-14,304, rilmenidine and clonidine, were non-selective or showed minor selectivity for α_2A- or α_2A-adrenoceptors. Moreover, using Monte Carlo simulations, we showed that the three-curve method gives more accurate estimates of drug binding constants for assays when two receptor sites arc present than methods analysing only one competition curve.

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Regular paperDelineation of rat kidney α2A- and α2B-adrenoeeptors with [3H]RX821002 radiollgand binding: computer modelling reveals that guanfacine is an α2A-selective compound

Abstract

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

J. Biol. Chem.

Eur. J. Pharmacol.

J. Biol. Chem.

J. Biol. Chem.

Life Sci.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Nonlinear Parameter Estimation

Guanine nucleotides regulutes both agonist and antagonist binding to cod brain α1-adrenoceptors

Acta Pharmacol. Toxicol.

Heterogeniety of α2-adrenoceptors in rat cortex but not human platelets can be defined by 8-OH-DPAT, RU 24969 and methysergide

Br. J. Pharmacol.

Subtypes of α2-adrenoceptors: Pharmacological and molcular biological evidence converge

Trends Pharmacol. Sci.

Alpha-2A and alpha-2B adrenergic receptor subtypes: antagonist binding in tissues and cell lines containing only one subtype

J. Pharmacol. Exp. Ther.

Molecular cloning, sequencing and expression of an α2-adrenergic receptor complementary DNA from rat brain

Mol. Cell. Biochem.

Functional evidence for heterogeneity of peripheral prejunctional α2-adrenoceptors

Br. J. Pharmacol.

Validation and statistical analysis of radioligand binding data for mixtures of pharmacological receptor subtypes

Mol. Pharmacol.

Regular paper
Delineation of rat kidney α_2A- and α_2B-adrenoeeptors with [³H]RX821002 radiollgand binding: computer modelling reveals that guanfacine is an α_2A-selective compound

Guanine nucleotides regulutes both agonist and antagonist binding to cod brain α₁-adrenoceptors

Heterogeniety of α₂-adrenoceptors in rat cortex but not human platelets can be defined by 8-OH-DPAT, RU 24969 and methysergide

Subtypes of α₂-adrenoceptors: Pharmacological and molcular biological evidence converge

Molecular cloning, sequencing and expression of an α₂-adrenergic receptor complementary DNA from rat brain

Functional evidence for heterogeneity of peripheral prejunctional α₂-adrenoceptors