胞二磷胆碱对乙酰胆碱诱导的大鼠灌流颈动脉血管床舒张的影响。

Effects of CDP-choline on acetylcholine-induced relaxation of the perfused carotid vascular beds of the rat.

Pinardi G, Pelissier T, Kramer V, Paeile C, Miranda H F

Department of Experimental Medicine Occident, Faculty of Medicine, University of Chile, Santiago.

Gen Pharmacol. 1994 Jul;25(4):635-8. doi: 10.1016/0306-3623(94)90239-9.

Abstract

The effects of an infusion of cytidine-5'-diphosphocholine (CDP-choline) on the relaxation induced by exogenous acetylcholine (ACh) was studied in the isolated and perfused external (ECB) and internal (ICB) carotid vascular beds of the rat. Changes in perfusion pressure were recorded during a dose-response curve to ACh and after a 30 min perfusion with CDP-choline (1 mg/min). 2. ACh induced a dose-dependent relaxation in both vascular beds, indicating the presence of muscarinic receptors. The affinity of the receptors for ACh in the ICB was significantly lower than in the ECB (ED50: 120 +/- 21.4 ng and 69 +/- 10.3 ng, respectively). 3. In the ICB the infusion of CDP-choline for 30 min significantly shifted the dose-response curve to ACh to the left, potentiating the relaxation. This effect was not seen in the ECB. 4. The infusion of hemicholinium (4 microM) for 30 min together with CDP-choline completely prevented the potentiation of exogenous ACh-induced relaxation in the ICB. 5. The results of the present work suggest that CDP-choline is acting by increasing choline levels in the cholinergic nerve terminals of the ICB, increasing the synthesis and/or release of ACh.

摘要

在大鼠离体灌注的颈外血管床（ECB）和颈内血管床（ICB）中，研究了输注胞苷-5'-二磷酸胆碱（CDP-胆碱）对外源性乙酰胆碱（ACh）诱导的舒张作用的影响。在ACh剂量-反应曲线期间以及用CDP-胆碱（1mg/min）灌注30分钟后，记录灌注压力的变化。2. ACh在两个血管床中均诱导剂量依赖性舒张，表明存在毒蕈碱受体。ICB中受体对ACh的亲和力显著低于ECB（ED50分别为120±21.4ng和69±10.3ng）。3. 在ICB中，输注CDP-胆碱30分钟可使ACh的剂量-反应曲线显著左移，增强舒张作用。在ECB中未观察到这种效应。4. 与CDP-胆碱一起输注30分钟的半胱氨酸（4μM）完全阻止了ICB中外源性ACh诱导的舒张增强。5. 本研究结果表明，CDP-胆碱的作用是通过提高ICB胆碱能神经末梢中的胆碱水平，增加ACh的合成和/或释放。