AstraZeneca R&D Mölndal, Integrative Pharmacology, Gastrointestinal Biology Mölndal, Mölndal, Sweden.
Pharmacology. 2010;85(5):272-9. doi: 10.1159/000285116. Epub 2010 Apr 7.
BACKGROUND/AIMS: Our aim was to investigate whether muscarinic and nicotinic receptors mediate nitric oxide release during motor events in the rat stomach.
Isolated rat stomach volume changes were monitored in an organ bath setup with an intragastric balloon coupled to a barostat and studied in basal conditions and during electrical vagal stimulation (EVS). In conscious rats, the intragastric pressure (IGP) was measured during test meal infusion.
In the presence of N(G)-nitro-L-arginine methyl ester (L-NAME; 0.1 mmol/l), EVS induced significant gastric contractions (mean +/- SEM = 0.27 +/- 0.04 ml; n = 6) that could be blocked by atropine (3 micromol/l) and hexamethonium (0.1 mmol/l). In the presence of atropine and/or hexamethonium, EVS-induced relaxations could not be blocked by L-NAME, while exogenous nitric oxide could still relax the stomach. In conscious rats, atropine (1 mg kg(-1)) initially decreased IGP, while during further distension it increased IGP. In the presence of L-NAME (30 mg kg(-1)) atropine consistently decreased IGP. L-NAME alone significantly increased IGP during the test meal infusion, but this effect was reduced in the presence of atropine.
These findings indicate a role for nicotinic and muscarinic receptors in the vagal-stimulation-induced activation of nitrergic nerves in the rat stomach.
背景/目的：我们的目的是研究毒蕈碱和烟碱受体是否在大鼠胃的运动事件中介导一氧化氮的释放。
在与压力计相连的器官浴装置中监测分离的大鼠胃容积变化，并在基础条件下和电刺激迷走神经（EVS）期间进行研究。在清醒大鼠中，在测试餐输注期间测量胃内压（IGP）。
在 N(G)-硝基-L-精氨酸甲酯（L-NAME；0.1 mmol/l）存在下，EVS 诱导明显的胃收缩（平均值 +/- SEM = 0.27 +/- 0.04 ml；n = 6），可被阿托品（3 微摩尔/l）和六烃季铵（0.1 mmol/l）阻断。在存在阿托品和/或六烃季铵的情况下，EVS 诱导的松弛不能被 L-NAME 阻断，而外源性一氧化氮仍能使胃松弛。在清醒大鼠中，阿托品（1 mg/kg(-1)) 最初降低 IGP，而在进一步扩张时增加 IGP。在 L-NAME（30 mg/kg(-1)) 存在下，阿托品一致地降低 IGP。L-NAME 单独在测试餐输注期间显着增加 IGP，但在存在阿托品的情况下，这种作用会降低。
这些发现表明毒蕈碱和烟碱受体在大鼠胃的迷走神经刺激诱导的氮能神经激活中起作用。
