Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University Plovdiv, Plovdiv, Bulgaria.
Department of Organic Chemistry, Faculty of Chemistry, University of Plovdiv, Plovdiv, Bulgaria.
Folia Med (Plovdiv). 2020 Sep 30;62(3):532-538. doi: 10.3897/folmed.62.e47844.
Examination of the potential possibilities of 2-chloro-N-(1-(3,4-dimethoxyphenyl)propan-2-yl)-2-phenylacetamide (IQP) to affect bioelectrogenesis and the contractile activity of isolated smooth muscles (SM) from stomach.
Having in mind the structural similarities between the molecules of papaverine and IQP, the aim of the present study was to examine such features of the newly synthesized molecule that may potentially affect the muscle tonus, spontaneous bioelectrical and contractile activities of smooth muscles isolated from the stomach, basing on specific mechanisms of papaverine.
The synthesis of IQP is based on the initially formed aziridine ring by principles of Gilbert's reaction. Impact of IQP on the bioelectrogenesis and the contractile activity of isolated smooth muscles from male Wistar rats was measured by the single sucrose-gap method and isometrically recorded.
IQP (1×10-5 - 2.5×10-4 mol/l) causes muscle relaxation, producing changes in two processes that have influence on the mechanical activity of smooth muscles:1. Blocked Ca2+ influx through the potential-dependent membrane Ca2+ channels, followed in turn by lowering the Ca2+ intracellular levels. This effect is proved by the changes in the frequency and amplitude of spike-potentials in sucrose-bridge experiments when IQP is applied.2. Activation of a cAMP-dependent signal cascade. The relaxing effect of IQP was significantly reduced in the presence of KT5720(5×10-6 mol/l), an inhibitor of protein kinase A.
We assume that there might be interconnections between these two IQP-dependent processes, because PKA-dependent phosphorylation of the L-type Ca2+ channels in smooth muscles provokes a reaction of inactivation.
研究 2-氯-N-(1-(3,4-二甲氧基苯基)丙-2-基)-2-苯基乙酰胺 (IQP) 对胃分离平滑肌的生物电发生和收缩活性的潜在可能性。
鉴于罂粟碱和 IQP 分子之间的结构相似性，本研究旨在根据罂粟碱的特定机制，检查新合成分子可能影响胃分离平滑肌的肌肉紧张度、自发生物电和收缩活性的特征。
IQP 的合成基于 Gilbert 反应的最初形成的氮丙啶环。通过单蔗糖间隙法和等长记录测量 IQP 对雄性 Wistar 大鼠分离平滑肌的生物电发生和收缩活性的影响。
IQP（1×10-5-2.5×10-4 mol/l）引起肌肉松弛，导致对平滑肌机械活动有影响的两个过程发生变化：1. 阻断通过电位依赖性膜 Ca2+通道的 Ca2+内流，随后细胞内 Ca2+水平降低。当 IQP 施加时，在蔗糖桥实验中，通过改变尖峰电位的频率和幅度证明了这种效应。2. cAMP 依赖性信号级联的激活。当存在蛋白激酶 A 抑制剂 KT5720（5×10-6 mol/l）时，IQP 的松弛作用明显降低。
我们假设这两个 IQP 依赖过程之间可能存在联系，因为平滑肌中 L 型 Ca2+通道的 PKA 依赖性磷酸化会引发失活反应。
