Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan.
Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan.
Gen Comp Endocrinol. 2022 Oct 1;327:114074. doi: 10.1016/j.ygcen.2022.114074. Epub 2022 Jun 11.
Cholecystokinin (CCK) is a peptide hormone mainly secreted by small intestinal endocrine I-cells and functions as a regulator of gallbladder contraction, gastric emptying, gastrointestinal (GI) motility, and satiety. The cellular effects of CCK in these peripheral tissues are predominantly mediated via CCK-A receptors which are found in smooth muscles, enteric neurons, and vagal afferent neurons in humans and animal models. Although various functions of CCK have been reported to be neurally mediated, it can also stimulate contraction via the CCK receptor on the smooth muscle. However, the entire underlying neural and cellular mechanisms involved in CCK-induced GI contractions are not clearly understood. Here, we first determined the cDNA and amino acid sequences of CCK and CCK-A receptor along with the distributions of cck mRNA and CCK-producing cells in house musk shrew (Suncus murinus, the laboratory strain named as suncus) and examined the mechanism of CCK-induced contraction in the GI tract. Mature suncus CCK-8 was identical to other mammalian species tested here, and suncus CCK-A receptor presented high nucleotide and amino acid homology with that of human, dog, mouse, and rat, respectively. Suncus CCK mRNA and CCK-producing cells were found mainly in small intestine and colon. In the organ bath study, CCK-8 induced dose-dependent contractions in the suncus stomach, duodenum, and jejunum, and these contractions were inhibited by atropine and CCK-A receptor antagonist. These results suggest that CCK-8-induced contraction is mediated in the myenteric cholinergic neural network and that CCK-A receptor is partly responsible for CCK-8-induced contractions. This study indicates that suncus is a useful animal model to study the functions of CCK involved in GI motility.
胆囊收缩素（CCK）是一种主要由小肠内分泌 I 细胞分泌的肽类激素，作为胆囊收缩、胃排空、胃肠（GI）运动和饱腹感的调节剂。CCK 在这些外周组织中的细胞效应主要通过 CCK-A 受体介导，该受体存在于人类和动物模型的平滑肌、肠神经元和迷走传入神经元中。尽管已经报道了 CCK 的各种功能是通过神经介导的，但它也可以通过平滑肌上的 CCK 受体刺激收缩。然而，CCK 诱导的 GI 收缩所涉及的完整神经和细胞机制尚不清楚。在这里，我们首先确定了 CCK 和 CCK-A 受体的 cDNA 和氨基酸序列，以及 cck mRNA 和产生 CCK 的细胞在小家鼠（Suncus murinus，实验室命名为 suncus）中的分布，并研究了 CCK 诱导 GI 收缩的机制。成熟的小家鼠 CCK-8 与这里测试的其他哺乳动物物种相同，小家鼠 CCK-A 受体与人类、狗、小鼠和大鼠的核苷酸和氨基酸同源性很高。小家鼠 CCK mRNA 和产生 CCK 的细胞主要存在于小肠和结肠中。在器官浴研究中，CCK-8 诱导小家鼠胃、十二指肠和空肠产生剂量依赖性收缩，这些收缩被阿托品和 CCK-A 受体拮抗剂抑制。这些结果表明，CCK-8 诱导的收缩是由肌间胆碱能神经网络介导的，CCK-A 受体部分负责 CCK-8 诱导的收缩。这项研究表明，小家鼠是研究与 GI 运动相关的 CCK 功能的有用动物模型。
