Department of Physiology, College of Medicine, Chosun University, Gwangju, Republic of Korea.
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea.
Cell Mol Biol (Noisy-le-grand). 2023 Feb 28;69(2):67-73. doi: 10.14715/cmb/2023.69.2.11.
Adenosine plays an important role on gastrointestinal (GI) motility through adenosine receptors. Interstitial cells of Cajal (ICC) are pacemaker cells that regulate GI smooth muscle activity. The functional role and its signal mechanism of adenosine on the pacemaker activity were investigated using whole-cell patch clamp, RT-PCR, and intracellular Ca2+-imaging with ICC from mouse colon. Adenosine depolarized the membrane potentials and increased the pacemaker potential frequency, which was blocked by a selective A1-receptor antagonist, but not A2a-, A2b, or A3-receptor antagonist. A selective A1 receptor agonist represented similar effects as those of adenosine and mRNA transcript of A1-receptor was expressed in ICC. The adenosine-induced effects were blocked by phospholipase C (PLC) and a Ca2+-ATPase inhibitor. Adenosine increased spontaneous intracellular Ca2+ oscillations, as seen fluo4/AM. Both hyperpolarization-activated cyclic nucleotide (HCN) channel inhibitors and adenylate cyclase inhibitors blocked the adenosine-induced effects. And adenosine increased the basal cellular adenylate cyclase activity in colonic ICC. However, adenosine and adenylate cyclase inhibitors did not show any influence on pacemaker activity in small intestinal ICC for a comparison with that of the small intestine. These results suggest adenosine modulates the pacemaker potentials by acting HCN channels- and intracellular Ca2+- dependent mechanisms through A1-receptor. Therefore, adenosine may be a therapeutic target in colonic motility disorders.
腺苷通过腺苷受体在胃肠道（GI）动力中发挥重要作用。Cajal 间质细胞（ICC）是调节 GI 平滑肌活动的起搏细胞。使用来自小鼠结肠的全细胞膜片钳、RT-PCR 和细胞内 Ca2+成像技术，研究了腺苷对起搏活动的功能作用及其信号机制。腺苷使膜电位去极化并增加起搏电位频率，这可被选择性 A1 受体拮抗剂阻断，但不能被 A2a、A2b 或 A3 受体拮抗剂阻断。选择性 A1 受体激动剂表现出与腺苷相似的作用，并且 ICC 中表达 A1 受体的 mRNA 转录本。腺苷诱导的作用被磷脂酶 C（PLC）和钙 ATP 酶抑制剂阻断。腺苷增加了自发的细胞内 Ca2+振荡，如 fluo4/AM 所见。HCN 通道抑制剂和腺苷酸环化酶抑制剂均阻断了腺苷诱导的作用。并且腺苷增加了结肠 ICC 中的基础细胞腺苷酸环化酶活性。然而，与小肠 ICC 相比，腺苷和腺苷酸环化酶抑制剂对起搏活性没有任何影响。这些结果表明，腺苷通过 A1 受体作用于 HCN 通道和细胞内 Ca2+依赖性机制来调节起搏电位。因此，腺苷可能是治疗结肠运动障碍的靶点。
