Arner P, Hellmér J, Wennlund A, Ostman J, Engfeldt P
Department of Medicine, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
Eur J Pharmacol. 1988 Jan 27;146(1):45-56. doi: 10.1016/0014-2999(88)90485-2.
The relationship between lipolysis and adrenoceptor occupancy was determined in isolated human fat cells, which possess both lipolytic beta-adrenoceptors and antilipolytic alpha 2-adrenoceptors. The beta-adrenoceptor agonist, isoprenaline, and the alpha 2-adrenoceptor agonist, clonidine, had lower affinities to compete with antagonist radioligands (Ki) than to affect the rate of lipolysis (Ka). At 1 min of incubation human fat cells bound isoprenaline and clonidine with high affinity to beta- and alpha 2-adrenoceptors, respectively, but this high-affinity binding rapidly converted to a low-affinity state. The relationship between lipolysis and adrenoceptor occupancy was also assessed after long-lasting receptor inactivation. The inactivation of a small receptor fraction shifted the dose-response curves for isoprenaline and clonidine to the right but did not alter the maximum effect of the agonists (responsiveness). These results suggest that alpha 2- and beta-adrenoceptors are coupled to lipolysis according to similar models. There is a non-linear relationship between receptor and effector for both receptors, which can be explained by the co-existence of spare receptors and a transient high-affinity state of the receptors for agonists.
在分离出的人体脂肪细胞中测定了脂解作用与肾上腺素能受体占有率之间的关系，这些细胞同时拥有脂解性β - 肾上腺素能受体和抗脂解性α₂ - 肾上腺素能受体。β - 肾上腺素能受体激动剂异丙肾上腺素和α₂ - 肾上腺素能受体激动剂可乐定与拮抗剂放射性配体竞争的亲和力（Ki）低于其对脂解速率的影响（Ka）。在孵育1分钟时，人体脂肪细胞分别以高亲和力与β - 和α₂ - 肾上腺素能受体结合异丙肾上腺素和可乐定，但这种高亲和力结合迅速转变为低亲和力状态。在受体长期失活后，也评估了脂解作用与肾上腺素能受体占有率之间的关系。一小部分受体失活使异丙肾上腺素和可乐定的剂量 - 反应曲线右移，但未改变激动剂的最大效应（反应性）。这些结果表明，α₂ - 和β - 肾上腺素能受体根据相似的模型与脂解作用相偶联。两种受体的受体与效应器之间均存在非线性关系，这可以通过备用受体的共存以及受体对激动剂的短暂高亲和力状态来解释。
