Glaza Izabela, Szadujkis-Szadurski Leszek, Szadujkis-Szadurski Rafał, Gajdus Marta, Olkowska Joanna
Department of Pharmacology and Therapy, Collegium Medicum in Bydgoszcz.
Postepy Hig Med Dosw (Online). 2011 Aug 3;65:478-81. doi: 10.5604/17322693.954785.
The subject of the study was determination of the effect of drugs on ileal smooth muscle contraction induced by activation of M(1) type muscarinic receptors. Drugs that have an effect on muscarinic receptors are divided to agonists, with close ties to the receptor and high internal activity and antagonists, with no internal activity. Conducted experiments tested interactions between a broad-spectrum agonist of muscarinic receptors, carbachol and a selective muscarinic receptor antagonist of M(1) type, pirenzepine.
MATERIAL/METHODS: Testing was conducted on tissues isolated from rat's intestine. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg). Concentration-effect curves were determined with the use of cumulated concentration method, in accordance with the van Rossum method (1963) in Kenakin modification (2006).
The purpose of the study was determination of concentration-effect curves for carbachol. This curve was compared with the curve of receptor occupation depending on concentration of this drug. Based on concentration-effect curves, the average value of EC(50) was calculated for carbachol, amounting to 2.44×10(-6) [M/l].
The results confirmed that atropine is effective in stopping contractions caused by carbachol, meeting the conditions of competitive antagonists. Atropine caused the shift of curves for carbachol to the right. Pirenzepine, selectively blocking muscarinic receptors of M(1) type gave similar results. It was proved that in the preparation of gastric fundus smooth muscle, M(1) type receptors occur not only presynaptically, but also postsynaptically.
本研究的主题是测定药物对由M（1）型毒蕈碱受体激活所诱导的回肠平滑肌收缩的影响。对毒蕈碱受体有作用的药物分为激动剂（与受体联系紧密且内在活性高）和拮抗剂（无内在活性）。所进行的实验测试了毒蕈碱受体的广谱激动剂卡巴胆碱与M（1）型选择性毒蕈碱受体拮抗剂哌仑西平之间的相互作用。
材料/方法：在从大鼠肠道分离出的组织上进行测试。体重在220克至360克之间的雄性Wistar大鼠通过腹腔注射乌拉坦（120毫克/千克）进行麻醉。根据van Rossum方法（1963年）并经Kenakin修改（2006年），采用累积浓度法测定浓度-效应曲线。
本研究的目的是测定卡巴胆碱的浓度-效应曲线。将该曲线与取决于该药物浓度的受体占有率曲线进行比较。根据浓度-效应曲线，计算出卡巴胆碱的EC（50）平均值为2.44×10（-6）[摩尔/升]。
结果证实阿托品可有效阻止由卡巴胆碱引起的收缩，符合竞争性拮抗剂的条件。阿托品使卡巴胆碱的曲线向右移动。选择性阻断M（1）型毒蕈碱受体的哌仑西平给出了类似结果。已证明在胃底平滑肌制剂中，M（1）型受体不仅存在于突触前，也存在于突触后。
