Okruhlicová L, Slezák J
Institute of Experimental Surgery, Slovak Academy of Sciences, Bratislava.
Physiol Bohemoslov. 1990;39(2):151-5.
Experiments using a cytochemical method showed the presence of a specific precipitate of the adenylate cyclase (AC) reaction on the sarcolemma and in the subsarcolemmal cisternae and junctional sarcoplasmic reticulum in rat cardiomyocytes. The localization of AC in the given organelles draws attention to the mutual association between Ca2+ ions and cAMP in the modulation of cardiac contractions. Trifluoperazine (TFP) and chlorpromazine (CHP) are known as phenothiazine derivatives inhibiting cellular enzymatic processes dependent on calmodulin and Ca2+. AC is one of these enzyme systems. The administration of TFP and CHP (both in a dose of 0.1 and 3 mmol.1(-1)) did not affect the cytochemical localization of the enzyme. Quantitative determination of 125I-cAMP by RIA showed that CHP inhibited AC activity in both concentrations. TFP, on the other hand, did not inhibit AC activity in 0.1 mmol.1(-1) concentration and actually stimulated its activation in 3 mmol.1(-1) concentration. The different action of the phenothiazine derivatives on AC activity can be attributed partly to the different affinity of TFP and CHP for calmodulin and partly to interaction of the inhibitor-calmodulin complex with the phosphodiesterase (PDE) system.
运用细胞化学方法进行的实验表明，大鼠心肌细胞的肌膜、肌膜下池和连接肌浆网中存在腺苷酸环化酶（AC）反应的特异性沉淀物。AC在这些细胞器中的定位使人关注到Ca2+离子与cAMP在心脏收缩调节中的相互关联。三氟拉嗪（TFP）和氯丙嗪（CHP）是已知的抑制依赖钙调蛋白和Ca2+的细胞酶促过程的吩噻嗪衍生物。AC就是这些酶系统之一。给予TFP和CHP（剂量均为0.1和3 mmol·L-1）并不影响该酶的细胞化学定位。通过放射免疫分析法定量测定125I-cAMP表明，两种浓度的CHP均抑制AC活性。另一方面，0.1 mmol·L-1浓度的TFP不抑制AC活性，而在3 mmol·L-1浓度时实际上刺激了其激活。吩噻嗪衍生物对AC活性的不同作用部分可归因于TFP和CHP对钙调蛋白的不同亲和力，部分可归因于抑制剂-钙调蛋白复合物与磷酸二酯酶（PDE）系统的相互作用。
