Herbette L, Napolitano C A, Messineo F C, Katz A M
Adv Myocardiol. 1985;5:333-46.
The nonspecific interactions of propranolol, timolol, and ethanol with model and sarcoplasmic reticulum membranes were determined utilizing radioisotopic association differential scanning calorimetry, and neutron diffraction. Differential scanning calorimetry performed on mixtures of these amphiphilic compounds and model membrane bilayers composed of dimyristoyllecithin showed that propranolol was approximately 25 times more lipid-soluble than timolol and at least 100 times more lipid-soluble than ethanol. Neutron diffraction showed that the solvation of propranolol was within the fatty acyl chain region of the lipid bilayer. This solvation correlated with the effect of propranolol to inhibit ATP-dependent calcium transport in isolated rabbit skeletal muscle sarcoplasmic reticulum, a membrane that lacks beta-adrenergic receptors. In contrast, the major site of interaction of ethanol was within the aqueous compartment hydrating the sarcoplasmic reticulum membrane. A model for nonspecific drug interaction with the sarcoplasmic reticulum membrane based on the site of interaction of these amphiphiles and their relative potencies to inhibit calcium transport by these membranes is proposed. In principle, this model could be extended to specific drug interactions with membranes.
利用放射性同位素结合差示扫描量热法和中子衍射法，测定了普萘洛尔、噻吗洛尔和乙醇与模型膜及肌浆网膜的非特异性相互作用。对这些两亲性化合物与由二肉豆蔻酰卵磷脂组成的模型膜双层混合物进行差示扫描量热法研究表明，普萘洛尔的脂溶性约为噻吗洛尔的25倍，至少是乙醇的100倍。中子衍射显示，普萘洛尔的溶剂化作用发生在脂质双层的脂肪酰链区域内。这种溶剂化作用与普萘洛尔抑制离体兔骨骼肌肌浆网中ATP依赖的钙转运的作用相关，该膜缺乏β-肾上腺素能受体。相比之下，乙醇的主要相互作用位点位于使肌浆网膜水合的水相区。基于这些两亲物的相互作用位点及其抑制这些膜钙转运的相对效力，提出了一个非特异性药物与肌浆网膜相互作用的模型。原则上，该模型可扩展到药物与膜的特异性相互作用。
