Rhythmic changes in colonic motility are regulated by period genes

Area of Science:

• Chronobiology
• Gastroenterology
• Molecular Biology

Background:

• Human bowel movements exhibit diurnal patterns, indicating biological clock involvement in colonic motility.
• While central biological clock mechanisms are understood, peripheral rhythmicity, particularly in the colon, remains less explored.

Purpose of the Study:

• To investigate the role of clock genes, specifically period 1 (per1) and period2 (per2), in regulating rhythmic colonic motility.
• To elucidate the underlying mechanisms, including the involvement of neuronal nitric oxide synthase (nNOS), in these rhythmic changes.

Main Methods:

• Organ bath studies, intracolonic pressure measurements, and stool output analysis were performed in wild-type and per1per2 double-knockout mice.
• Neuronal nitric oxide synthase (nNOS) knockout mice and pharmacological inhibition were used to examine the nNOS pathway's role.

Main Results:

• Wild-type mice exhibited rhythmic colonic motility and circular muscle contractility, peaking at the onset of night.
• Rhythmicity was abolished in per1per2 double-knockout mice, indicating a crucial role for these clock genes.
• Colonic circular muscle contractility rhythmicity was also abolished in nNOS knockout mice and with nNOS inhibition, highlighting the nNOS pathway's importance.

Conclusions:

• Clock genes (per1 and per2) are essential regulators of colonic motility rhythms.
• A neuronal nitric oxide synthase (nNOS)-mediated inhibitory process is involved in colonic motility rhythms.
• These findings reveal a connection between biological clock genes and the nNOS pathway in governing colonic motor function.