Percy William H, Keupp Sarah M
Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD 57069-2390, USA.
J Pharm Pharmacol. 2008 Aug;60(8):1097-103. doi: 10.1211/jpp.60.8.0016.
We have investigated adrenoceptor-mediated responses of muscularis mucosae from the proximal, mid and distal regions of the rat colon. Noradrenaline-induced relaxations of the muscularis mucosae in each region were unaffected by atenolol, butoxamine or propranolol, but they were attenuated by the selective beta3-adrenoceptor antagonist cyanopindolol. The beta3-adrenoceptor agonist CL216343 elicited concentration-dependent relaxation of the muscularis mucosae in all regions of the colon. Isoprenaline, a non-selective beta-adrenoceptor agonist, evoked concentration-dependent relaxations of the muscularis mucosae in all regions, but only in the proximal colon were these significantly larger than the maximum noradrenaline-induced relaxation. The alpha1-adrenoceptor agonist methoxamine caused large contractions of the proximal colonic muscularis mucosae. When proximal tissue was pretreated with phentolamine, an alpha1-adrenoceptor antagonist, maximal noradrenaline- and isoprenaline-induced relaxations did not differ significantly. Although the mid colonic muscularis mucosae was also found to possess excitatory alpha1-adrenoceptors, these were associated with small contractions and did not modify the muscle's inhibitory responses to noradrenaline. Distal colonic muscularis mucosae lacked excitatory adrenoceptors and only responded to noradrenaline with beta3-adrenoceptor-mediated relaxations. No evidence was obtained for functional alpha2-adrenoceptors on the muscularis mucosae in any region of the rat colon. These data demonstrated that noradrenaline-induced relaxation of the rat colonic muscularis mucosae was mediated via beta3-adrenoceptors throughout, but in the proximal region this was modified by concurrent excitatory alpha1-adrenoceptor activation. Based upon these observations it appeared unlikely that noradrenaline-induced relaxation of rat colonic muscularis mucosae would be functionally linked to the secretory responses of the corresponding mucosa during periods of increased sympathetic activity.
我们研究了大鼠结肠近端、中段和远端区域黏膜肌层的肾上腺素能受体介导的反应。去甲肾上腺素诱导的各区域黏膜肌层舒张不受阿替洛尔、丁氧胺或普萘洛尔的影响，但被选择性β3肾上腺素能受体拮抗剂氰吲哚洛尔减弱。β3肾上腺素能受体激动剂CL216343在结肠所有区域均引起黏膜肌层浓度依赖性舒张。非选择性β肾上腺素能受体激动剂异丙肾上腺素在所有区域均引起黏膜肌层浓度依赖性舒张，但仅在近端结肠，这些舒张显著大于去甲肾上腺素诱导的最大舒张。α1肾上腺素能受体激动剂甲氧明引起近端结肠黏膜肌层的强烈收缩。当用α1肾上腺素能受体拮抗剂酚妥拉明预处理近端组织时，去甲肾上腺素和异丙肾上腺素诱导的最大舒张无显著差异。尽管中段结肠黏膜肌层也被发现具有兴奋性α1肾上腺素能受体，但这些受体与小收缩相关，且不改变肌肉对去甲肾上腺素的抑制反应。远端结肠黏膜肌层缺乏兴奋性肾上腺素能受体，仅通过β3肾上腺素能受体介导的舒张对去甲肾上腺素产生反应。在大鼠结肠任何区域的黏膜肌层均未获得功能性α2肾上腺素能受体的证据。这些数据表明，去甲肾上腺素诱导的大鼠结肠黏膜肌层舒张全程通过β3肾上腺素能受体介导，但在近端区域，这一过程被同时发生的兴奋性α1肾上腺素能受体激活所改变。基于这些观察结果，在交感神经活动增加期间，去甲肾上腺素诱导的大鼠结肠黏膜肌层舒张在功能上似乎不太可能与相应黏膜的分泌反应相关联。
