Brandt H D, Meyer C L
Department of Pharmacology, Potchefstroom University, South Africa.
Arch Int Pharmacodyn Ther. 1987 Sep;289(1):46-59.
The affinity (pA2 or pKB) values of 3 different beta-adrenoceptor blocking drugs were determined using the isolated guinea-pig tracheal chain preparation. The pA2 values for each of the beta-adrenoceptor blocking drugs were determined, using respectively isoprenaline and salbutamol as agonists. Neuronal and extraneuronal uptake of agonist were blocked with phenoxybenzamine. With isoprenaline, a nonselective beta-adrenoceptor agonist, the pA2 values for the blocking drugs were unacceptable. Using the beta 2-selective beta-adrenoceptor agonist, salbutamol, under the same conditions, resulted in consistent pA2 values for the nonselective beta-adrenoceptor blocking drug propranolol and some concentrations of the beta 2-selective blocking drug ICI 118.551. pA2 Values for the beta1-selective antagonist atenolol were not consistent for the concentrations used. It is suggested that this is due to the guinea-pig trachea having a mixed beta-adrenoceptor population. A mathematical model is presented that shows the influence of a mixed receptor subpopulation on the shift of theoretical agonist concentration-effect curves in the presence of a competitive antagonist. It can be shown that the affinity values of antagonists for a specific receptor subtype are to a greater or lesser degree unreliable, depending upon the selectivity-ratios of both the agonist and the antagonist used.
使用离体豚鼠气管链制备物测定了3种不同β-肾上腺素能受体阻断药物的亲和力（pA2或pKB）值。分别以异丙肾上腺素和沙丁胺醇作为激动剂，测定了每种β-肾上腺素能受体阻断药物的pA2值。用酚苄明阻断激动剂的神经元和非神经元摄取。对于非选择性β-肾上腺素能激动剂异丙肾上腺素，阻断药物的pA2值不可接受。在相同条件下，使用β2选择性β-肾上腺素能激动剂沙丁胺醇，得到了非选择性β-肾上腺素能阻断药物普萘洛尔以及某些浓度的β2选择性阻断药物ICI 118.551的一致pA2值。对于所用浓度，β1选择性拮抗剂阿替洛尔的pA2值不一致。提示这是由于豚鼠气管具有混合的β-肾上腺素能受体群体。提出了一个数学模型，该模型显示了在存在竞争性拮抗剂的情况下，混合受体亚群对理论激动剂浓度-效应曲线位移的影响。可以证明，拮抗剂对特定受体亚型的亲和力值或多或少是不可靠的，这取决于所用激动剂和拮抗剂的选择性比率。
