Purinergic ATP-P2X7 Signaling Drives Colonic Giant Migrating Contraction in Suncus murinus

Giant migrating contractions (GMCs) in the colon play a critical role in propelling the intraluminal contents and facilitating defecation. However, the regulatory mechanisms underlying GMCs remain unclear. This study aimed to identify the factors regulating GMC activity and to elucidate the mechanism of colonic GMCs using conscious Suncus murinus (suncus), an animal model for colonic motility. In vivo, intravenous administration of 5-200 mg/kg adenosine triphosphate (ATP) induced strong GMC-like contractions with contractile traces closely resembling spontaneous GMCs. Pretreatment with P2X7 receptor antagonists markedly suppressed ATP-induced GMCs. Moreover, a potent P2X7 receptor agonist evoked GMC-like contractions. ATP-induced GMCs were also inhibited by atropine. In vitro, cumulative ATP failed to induce colonic contractions. Collectively, our findings identified purinergic ATP as a novel regulator of GMCs and demonstrated that ATP activates cholinergic neurons via P2X7 receptors to trigger contractions. Modulation of ATP-mediated signaling may represent a potential therapeutic strategy for impaired colonic motility disorders.