2,6-二丁基苄胺（B25）在大鼠离体输精管、心脏和平滑肌制剂中的钙调节特性。

Calcium modulatory properties of 2,6-dibutylbenzylamine (B25) in rat isolated vas deferens, cardiac and smooth muscle preparations.

作者信息

Pirisino R, Banchelli G, Ignesti G, Mantelli L, Matucci R, Raimondi L, Buffoni F

机构信息

Department of Pharmacology, University of Florence, Italy.

出版信息

Br J Pharmacol. 1993 Aug;109(4):1038-45. doi: 10.1111/j.1476-5381.1993.tb13726.x.

DOI:10.1111/j.1476-5381.1993.tb13726.x

PMID:8401916

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2175720/

Abstract

In rat isolated vas deferens the new compound 2,6-dibutylbenzylamine (B25) evoked a series of repeating rhythmic contractions. Concentration-response curves constructed for this effect were bell-shaped, indicating a biphasic effect for this compound. By contrast, B25 depressed heart contractility without any visible positive inotropic or chronotropic activity. 2. Experiments with tetrodotoxin, reserpine, capsaicin, alpha-adrenoceptor blocking compounds and other agents permit us to exclude a release of neuromediators or a direct stimulation of post-synaptic receptors to account for the rhythmic effect of B25 in the rat vas deferens. 3. In the same tissue, the increase in 45Ca2+ uptake, the voltage-dependency as well as the dependence of the B25-induced rhythmic activity upon the external calcium concentration indicate a direct activation of voltage-sensitive calcium channels (VSCC). 4. Verapamil paradoxically stimulated the rhythmic effect of B25 in the rat vas deferens. La3+ was inactive while nifedipine was a weak inhibitor. By contrast Ni2+ and Mn2+ ions were good inhibitors (IC50 < 10(-4) M), suggesting that a possible opening of T-type VSCC underlies rhythmic effect of B25. 5. In radioligand binding studies competition experiments with [3H]-nitrendipine indicated that only at high concentrations was B25 able to interact with dihydropyridine-sensitive binding sites of heart and vas deferens smooth muscle. 6. B25 (3-30 microM) counteracted the inhibitory effects of omega-conotoxin GVIA in field-stimulated rat vas deferens.

摘要

在大鼠离体输精管中，新化合物2,6-二丁基苄胺（B25）引发了一系列重复性的节律性收缩。针对该效应构建的浓度-反应曲线呈钟形，表明该化合物具有双相效应。相比之下，B25降低了心脏收缩力，且无任何明显的正性肌力或变时活性。2. 用河豚毒素、利血平、辣椒素、α-肾上腺素能受体阻断化合物及其他药物进行的实验，使我们能够排除神经介质的释放或对突触后受体的直接刺激来解释B25在大鼠输精管中的节律性效应。3. 在同一组织中，45Ca2+摄取的增加、电压依赖性以及B25诱导的节律性活动对细胞外钙浓度的依赖性表明电压敏感性钙通道（VSCC）被直接激活。4. 维拉帕米反常地刺激了B25在大鼠输精管中的节律性效应。镧离子无活性，而硝苯地平是一种弱抑制剂。相比之下，镍离子和锰离子是良好的抑制剂（IC50 < 10(-4) M），提示T型VSCC的可能开放是B25节律性效应的基础。5. 在放射性配体结合研究中，用[3H]-尼群地平进行的竞争实验表明，仅在高浓度时B25才能与心脏和输精管平滑肌的二氢吡啶敏感结合位点相互作用。6. B25（3 - 30 microM）抵消了ω-芋螺毒素GVIA在电场刺激的大鼠输精管中的抑制作用。