Slánský J, Kadlec O, Masek K, Gulda O
Institute of Pharmacology, Academy of Sciences of the Czech Republic, Prague.
Pharmacology. 1994 Jan;48(1):11-20. doi: 10.1159/000139157.
The mode of action of muramyl dipeptide (MDP), a compound with immunopharmacological properties, was studied in isolated nerve smooth muscle preparations with different receptor systems. The amplitudes of contractions evoked directly by stimulants as well as neurogenic twitches or relaxations were registered. In the rat stomach strip EC50 of acetylcholine, serotonin (5-HT) and KCl was estimated. MDP (50 nmol/l) but not levamisole potentiated selectively the contractions evoked by 5-HT and significantly (p < 0.01) lowered the respective EC50. In the rat vas deferens MDP selectively potentiated the twitches enhanced by 5-HT but not those enhanced by noradrenaline. Such potentiation was blocked by 5-HT3 antagonists tropisetron and MDL 72,222 (1 alpha H,3 alpha,5 alpha-H-tropan-3-yl 3,5-dichlorobenzoate) but not by the 5-HT2 antagonist ketanserin. The antagonist methiothepin nonselectively abolished the potentiation by MDP as well as the enhancement of twitches by 5-HT and noradrenaline, whereas l-propranolol and isamoltan influenced neither the enhancement of twitches by 5-HT nor the potentiation by MDP. In the isolated longitudinal muscle of guinea pig proximal colon, 5-HT caused a biphasic response in the presence of atropine; the initial neurogenic relaxation was potentiated in the presence of MDP and was suppressed in the presence of tropisetron. Thus, the potentiating effect of MDP in the isolated organs studied was selective with respect to the serotoninergic system and might be mediated by 5-HT3 receptors.
对具有免疫药理学特性的化合物胞壁酰二肽（MDP）的作用方式，在具有不同受体系统的离体神经平滑肌制备物中进行了研究。记录了由兴奋剂直接诱发的收缩幅度以及神经源性抽搐或舒张的幅度。在大鼠胃条中，对乙酰胆碱、5-羟色胺（5-HT）和氯化钾的半数有效浓度（EC50）进行了评估。MDP（50纳摩尔/升）而非左旋咪唑选择性地增强了由5-HT诱发的收缩，并显著（p<0.01）降低了相应的EC50。在大鼠输精管中，MDP选择性地增强了由5-HT增强的抽搐，但未增强由去甲肾上腺素增强的抽搐。这种增强作用被5-HT3拮抗剂托烷司琼和MDL 72,222（1αH，3α，5α-H-托烷-3-基3,5-二氯苯甲酸酯）阻断，但未被5-HT2拮抗剂酮色林阻断。拮抗剂甲硫噻平非选择性地消除了MDP的增强作用以及5-HT和去甲肾上腺素对抽搐的增强作用，而普萘洛尔和异莫他明既不影响5-HT对抽搐的增强作用，也不影响MDP的增强作用。在豚鼠近端结肠的离体纵行肌中，在阿托品存在的情况下，5-HT引起双相反应；在MDP存在的情况下，初始的神经源性舒张增强，而在托烷司琼存在的情况下受到抑制。因此，MDP在所研究的离体器官中的增强作用对5-羟色胺能系统具有选择性，可能由5-HT3受体介导。
