A quantitative method of analyzing the interaction of slightly selective radioligands with multiple receptor subtypes.

摘要: Subclasses of receptors exist for most neurotransmitters. Frequently, two subtypes coexist in the same tissue and, some cases, they mediate physiological response. In tissues with classes binding sites a given hormone, an estimate proportion each class is obtained by inhibiting single concentration radioligand selective unlabeled ligand. Accurate estimates density will only be obtained, however, if entirely nonselective. Selectivity just 2- to 3-fold can markedly influence results subtype analysis. The conclusion that nonselective usually based on saturation curve. If Scatchard analysis such data linear plot, then it concluded However, cannot distinguish between and one slightly selective. use lead errors 50% or more, depending relative Kd values sites. A new analytical method has been developed used quantitate differences affinity distinct radioligand. This approach requires series inhibition experiments ligand performed presence increasing concentrations Analysis resulting curves, utilizing mathematical modeling program MLAB PROPHET system, yields accurate receptor as well labeled ligands. was determine whether 125I-iodopindolol shows selectivity beta 1- 2-adrenergic receptors. curves generated ligands ICI 89,406 (beta 1-selective) 118,551 2-selective), using membranes prepared from C6 glioma cells. These cells contain both 125I-Iodopindolol determined Since sensitivity this superior analysis, likely other radioligands, previously thought nonselective, shown when analyzed method.