Kobayashi Tsukasa, Takeba Yuko, Ootaki Masanori, Ohta Yuki, Kida Keisuke, Iiri Taroh, Matsumoto Naoki
Department of Pharmacology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan.
Cell Tissue Res. 2025 Jun;400(3):303-317. doi: 10.1007/s00441-025-03969-z. Epub 2025 Mar 27.
Constipation and other digestive disorders are common in older adults. The autonomic nervous system plays a critical role in regulating digestive motility in the intestinal tract. However, studies on age-related changes in autonomic function and receptor expression in the intestinal tract are limited. In this study, we examined the expression of neurotransmitter receptors in the autonomic nervous system and the effects of acetylcholine and β-agonists on intestinal contraction and relaxation in the jejunum of aged rats. Jejunal sections collected from male and female Wistar/ST rats aged 4, 11, and 18 months were analyzed. Immunohistochemical staining and enzyme-linked immunosorbent assay were used to measure the expression of muscarinic acetylcholine receptors (CHRM2 and CHRM3) and β-adrenergic receptors (β2-ADR and β3-ADR). The effects of acetylcholine, isoproterenol, and mirabegron were assessed in the isolated jejunum for each age group. There was no significant difference in CHRM2 receptor expression among the age groups; however, CHRM3 receptor expression decreased with age. Additionally, the sensitivity to acetylcholine-induced contractile responses decreased with age. Although β2-ADR receptor expression did not differ among the age groups, β3-ADR receptor expression increased with age. Despite this, the relaxation response to isoproterenol and mirabegron decreased with age. Our study revealed an age-related decrease in CHRM3 expression and the contractile response to acetylcholine in the small intestine of rats. Although β-ADR expression, particularly β3-ADR, increased with age, the relaxation response to β-adrenergic agonists gradually decreased.
便秘和其他消化系统疾病在老年人中很常见。自主神经系统在调节肠道消化蠕动方面起着关键作用。然而，关于肠道自主神经功能和受体表达随年龄变化的研究有限。在本研究中，我们检测了老年大鼠空肠自主神经系统中神经递质受体的表达，以及乙酰胆碱和β-激动剂对肠道收缩和舒张的影响。分析了从4个月、11个月和18个月大的雄性和雌性Wistar/ST大鼠收集的空肠切片。采用免疫组织化学染色和酶联免疫吸附测定法来测量毒蕈碱型乙酰胆碱受体（CHRM2和CHRM3）和β-肾上腺素能受体（β2-ADR和β3-ADR）的表达。评估了每个年龄组分离空肠中乙酰胆碱、异丙肾上腺素和米拉贝隆的作用。各年龄组之间CHRM2受体表达无显著差异；然而，CHRM3受体表达随年龄下降。此外，对乙酰胆碱诱导的收缩反应的敏感性随年龄下降。虽然各年龄组之间β2-ADR受体表达无差异，但β3-ADR受体表达随年龄增加。尽管如此，对异丙肾上腺素和米拉贝隆的舒张反应随年龄下降。我们的研究揭示了大鼠小肠中CHRM3表达以及对乙酰胆碱的收缩反应随年龄下降。虽然β-ADR表达，尤其是β3-ADR，随年龄增加，但对β-肾上腺素能激动剂的舒张反应逐渐下降。
