Shoshan-Barmatz V
Department of Biology, Ben Gurion University of the Negev, Beer Sheva, Israel.
Biochem J. 1988 Dec 15;256(3):733-9. doi: 10.1042/bj2560733.
Preincubation of sarcoplasmic reticulum (SR) with propranolol or tetracaine inhibits Ca2+ accumulation and stimulates ATPase activity by more than 2-fold. This effect is obtained only when the preincubation is carried out in the presence of ATP or other nucleoside triphosphates. The (ATP + drug)-induced inhibition of Ca2+ accumulation is pH-dependent, increasing as the pH rises above 7.5. The presence of micromolar concentrations of Ca2+ or Mg2+ during the preincubation prevents the inhibitory effect of ATP plus drug on Ca2+ accumulation or ATPase activity. The (ATP + drug) modification of SR vesicles resulted in stimulation of a rapid Ca2+ efflux from passively loaded vesicles. The ATP-dependent inhibition of Ca2+ accumulation by the drug is obtained with other local anaesthetics. The drug concentration required for 50% inhibition was 0.15 mM for dibucaine and 0.4 mM for both propranolol and tetracaine, whereas it was 5 mM, 8 mM and greater than 10 mM for lidocaine, benzocaine and procaine respectively. The heavy SR vesicles were only slightly affected by the incubation with propranolol or tetracaine in the presence of ATP, but their sensitivity increased markedly after storage at 0 degrees C for 24-48 h. These results suggest that propranolol and some local anaesthetics, in the presence of ATP, stimulate Ca2+ efflux by modifying a protein factor(s) rather than the phospholipid bilayer.
将肌浆网（SR）与普萘洛尔或丁卡因预孵育可抑制Ca2+蓄积，并使ATP酶活性提高2倍以上。仅当在ATP或其他核苷三磷酸存在下进行预孵育时，才会出现这种效应。（ATP + 药物）诱导的Ca2+蓄积抑制作用是pH依赖性的，随着pH升高至7.5以上而增强。预孵育期间存在微摩尔浓度的Ca2+或Mg2+可防止ATP加药物对Ca2+蓄积或ATP酶活性的抑制作用。（ATP + 药物）对SR囊泡的修饰导致被动加载囊泡中Ca2+快速外流。该药物对Ca2+蓄积的ATP依赖性抑制作用在其他局部麻醉药中也存在。二丁卡因50%抑制所需的药物浓度为0.15 mM，普萘洛尔和丁卡因均为0.4 mM，而利多卡因、苯佐卡因和普鲁卡因分别为5 mM、8 mM和大于10 mM。在ATP存在下，重SR囊泡与普萘洛尔或丁卡因孵育时仅受到轻微影响，但在0℃储存24 - 48小时后其敏感性显著增加。这些结果表明，在ATP存在下，普萘洛尔和一些局部麻醉药通过修饰一种或多种蛋白质因子而非磷脂双层来刺激Ca2+外流。
