Rhythmic changes in colonic motility are regulated by period genes.
Human bowel movements usually occur during the day and seldom during the night, suggesting a role for a biological clock in the regulation of colonic motility. Research has unveiled molecular and physiological mechanisms for biological clock function in the brain; less is known about peripheral rhythmicity. This study aimed to determine whether clock genes such as period 1 (per1) and period2 (per2) modulate rhythmic changes in colonic motility. Organ bath studies, intracolonic pressure measurements, and stool studies were used to examine measures of colonic motility in wild-type and per1per2 double-knockout mice. To further examine the mechanism underlying rhythmic changes in circular muscle contractility, additional studies were completed in neuronal nitric oxide synthase (nNOS) knockout mice. Intracolonic pressure changes and stool output in vivo, and colonic circular muscle contractility ex vivo, are rhythmic with greatest activity at the start of night in nocturnal wild-type mice. In contrast, rhythmicity in these measures was absent in per1per2 double-knockout mice. Rhythmicity was also abolished in colonic circular muscle contractility of wild-type mice in the presence of N(omega)-nitro-L-arginine methyl ester and in nNOS knockout mice. These findings suggest that rhythms in colonic motility are regulated by both clock genes and a nNOS-mediated inhibitory process and suggest a connection between these two mechanisms.
Hoogerwerf
Willemijntje A
WA
Department of Internal Medicine, Division of Gastroenterology, University of Michigan, VA Ann Arbor Healthcare System, 2215 Fuller Rd., Ann Arbor, MI 48105, USA. willemij@umich.edu
Shahinian
Vahakn B
VB
Cornélissen
Germaine
G
Halberg
Franz
F
Bostwick
Jonathon
J
Timm
John
J
Bartell
Paul A
PA
Cassone
Vincent M
VM
D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000502:physiology*; D003106:Colon / Q000294:innervation / Q000502:physiology*; D003624:Darkness; D003672:Defecation / Q000502:physiology; D004435:Eating; D005243:Feces; D005769:Gastrointestinal Motility / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000235:genetics* / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D017440:Photoperiod
C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse