Pesic S, Grbovic L, Stoiljkovic M, Nikolic V, Djokic J
Department of Pharmacology and Toxicology, University of Nis, School of Medicine, Nis, Serbia.
J Vet Pharmacol Ther. 2009 Apr;32(2):109-15. doi: 10.1111/j.1365-2885.2008.01008.x.
Acetylcholine interacts with endothelial muscarinic receptors releasing nitric oxide and causing vasodilatation. To identify the receptor subtype responsible for acetylcholine-induced relaxation in canine uterine artery, the usual organ bath method for in vitro investigation on isolated blood vessels was applied. Using a range of muscarinic receptor antagonists such as atropine (nonselective), pirenzepine (M(1)-selective), methoctramine (M(2)-selective) and p-fluoro-hexahydro-sila-difenidol (p-FHHSiD) (M(1)/M(3)) and determining pA2 value of those antagonists through Shild analysis, we aimed at establishing a precise receptor mechanism underlying acetylcholine-induced relaxation in isolated canine uterine artery. The relaxation of uterine arterial rings in response to acetylcholine in the presence or absence of selective muscarinic receptors antagonists was calculated using concentration response curves. Acetylcholine induced concentration-dependent and endothelium-dependent relaxation of arterial rings precontracted with phenylephrine (pEC(50) = 6.90 +/- 0.02). Muscarinic receptors antagonists atropine, pirenzepine, methoctramine and p-FHHSiD competitively antagonized the response to acetylcholine and obtained pA(2) values were 9.91 +/- 0.06, 6.60 +/- 0.04, 6.21 +/- 0.08 and 8.05 +/- 0.1, respectively. This study showed that acetylcholine induced endothelium-dependent relaxation of canine uterine artery by stimulation of muscarinic receptors localized on the endothelial cells. On the basis of differential antagonist affinity, we suggest that the muscarinic receptors involved in the acetylcholine-induced relaxation of canine uterine artery are predominantly of M(3) subtype.
乙酰胆碱与内皮毒蕈碱受体相互作用，释放一氧化氮并引起血管舒张。为了确定犬子宫动脉中负责乙酰胆碱诱导舒张的受体亚型，采用了体外研究离体血管常用的器官浴法。使用一系列毒蕈碱受体拮抗剂，如阿托品（非选择性）、哌仑西平（M(1)选择性）、甲溴东莨菪碱（M(2)选择性）和对氟六氢硅二苯醚（p-FHHSiD）（M(1)/M(3)），并通过希尔分析确定这些拮抗剂的pA2值，我们旨在建立犬离体子宫动脉中乙酰胆碱诱导舒张的精确受体机制。使用浓度反应曲线计算在存在或不存在选择性毒蕈碱受体拮抗剂的情况下，子宫动脉环对乙酰胆碱的舒张反应。乙酰胆碱诱导用去氧肾上腺素预收缩的动脉环产生浓度依赖性和内皮依赖性舒张（pEC(50)=6.90±0.02）。毒蕈碱受体拮抗剂阿托品、哌仑西平、甲溴东莨菪碱和p-FHHSiD竞争性拮抗对乙酰胆碱的反应，获得的pA(2)值分别为9.91±0.06、6.60±0.04、6.21±0.08和8.05±0.1。本研究表明，乙酰胆碱通过刺激内皮细胞上的毒蕈碱受体诱导犬子宫动脉的内皮依赖性舒张。基于不同的拮抗剂亲和力，我们认为参与乙酰胆碱诱导犬子宫动脉舒张的毒蕈碱受体主要是M(3)亚型。
