Narimatsu Naho, Saito Motoaki, Kazuyama Emi, Hisadome Yoshie, Kinoshita Yukako, Satoh Itaru, Okada Shin-Ichi, Suzuki Hiroto, Yamada Masashi, Satoh Keisuke
Department of Pathophysiological and Therapeutic Science, Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishimachi, Yonago.
Biomed Res. 2007 Oct;28(5):267-73. doi: 10.2220/biomedres.28.267.
We evaluated the effects of N-hexacosanol, a cyclohexenonic long-chain fatty alcohol, on muscarinic receptors in diabetic rat ileal dysfunction. Eight-week-old male SD rats were divided into four groups. After induction of diabetes (streptozotocin 50 mg/kg, i.p.), three groups were maintained for eight weeks with treatment by N-hexacosanol (0, 2 or 8 mg/kg, s.c. every day). Ileum function was investigated by organ bath studies using carbachol and KCl, and the expression levels of muscarinic M(2) and M(3) receptors were investigated by real-time polymerase chain reaction. Various concentrations of subtype-selective muscarinic antagonists, i.e., atropine (non-selective), pirenzepine (M(1) selective), methoctramine (M(2) selective), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M(1)/M(3) selective), were used in this study. In the presence and absence of these antagonists, contractile response curves to increasing concentrations of carbachol were investigated. Treatment with N-hexacosanol did not alter the diabetic status of the rats, but did significantly prevent the carbachol-induced hypercontractility in diabetic rat ileum. Estimation of the pA(2) values for atropine, pirenzepine, methoctramine, and 4-DAMP indicated that the carbacholinduced contractile response in the ileum is mainly mediated through the muscarinic M(3) receptor subtype in all groups. Furthermore, N-hexacosanol significantly prevented the diabetes-induced up-regulation of intestinal muscarinic M(2) and M(3) receptor mRNAs in streptozotocin-diabetic rats. Our data indicated that N-hexacosanol exerts preventive effects with respect to carbachol-induced hypercontractility in the diabetic rat ileum without qualitative alteration of the muscarinic receptor system.
我们评估了环己烯酸长链脂肪醇正二十六醇对糖尿病大鼠回肠功能障碍中毒蕈碱受体的影响。将8周龄雄性SD大鼠分为四组。诱导糖尿病（链脲佐菌素50mg/kg，腹腔注射）后，三组大鼠用正二十六醇（0、2或8mg/kg，皮下注射，每日一次）治疗8周。通过使用卡巴胆碱和氯化钾的器官浴研究来研究回肠功能，通过实时聚合酶链反应研究毒蕈碱M(2)和M(3)受体的表达水平。本研究使用了各种浓度的亚型选择性毒蕈碱拮抗剂，即阿托品（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4-二苯基乙酰氧基-N-甲基哌啶甲基碘化物（4-DAMP，M(1)/M(3)选择性）。在有和没有这些拮抗剂的情况下，研究了对浓度递增的卡巴胆碱的收缩反应曲线。用正二十六醇治疗并没有改变大鼠的糖尿病状态，但确实显著预防了糖尿病大鼠回肠中卡巴胆碱诱导的过度收缩。对阿托品、哌仑西平、甲溴东莨菪碱和4-DAMP的pA(2)值的估计表明，所有组中回肠中卡巴胆碱诱导的收缩反应主要通过毒蕈碱M(3)受体亚型介导。此外，正二十六醇显著预防了链脲佐菌素诱导的糖尿病大鼠肠道毒蕈碱M(2)和M(3)受体mRNA的糖尿病诱导上调。我们的数据表明，正二十六醇对糖尿病大鼠回肠中卡巴胆碱诱导的过度收缩具有预防作用，而不会对毒蕈碱受体系统进行定性改变。
