Characterization of the motor inhibitory role of colonic mucosa under chemical stimulation in mice

Abstract

Martín-Cano FE, Camello PJ, Pozo MJ. Characterization of the motor inhibitory role of colonic mucosa under chemical stimulation in mice. Am J Physiol Gastrointest Liver Physiol 306: G614 -G621, 2014. First published February 13, 2014 doi:10.1152/ajpgi.00208.2013The main roles of the colonic mucosa are the absorption of water and electrolytes and the barrier function that preserves the integrity of the colonic wall. The mediators and mechanisms to accomplish these functions are under continuous investigation, but little attention has been paid to a possible control of colonic motility by the mucosa that would fine tune the relationship between absorption and motility. The purpose of this study was to establish the role of the mucosa in the control of induced colonic contractility. Young ICR-CD1 mice (3-5 mo old) were studied. Isometric tension transducers were used to record contractility in fullthickness (FT) and mucosa-free (MF) strips from proximal colon. Proximal FT strips showed lower KCl-and bethanechol-induced responses than MF strips. The difference was not due to mechanical artefacts since the contractile response of FT strips to electrical field stimulation was around 50% lower than in MF. The inhibitory effects of the mucosa on FT strips were mimicked by immersion of separate strips of mucosa in the organ bath but not by addition of mucosal extract, suggesting gaseous molecules as mediators of this effect. Incubation of MF strips with synthase inhibitors of nitric oxide, carbon monoxide, and hydrogen sulfide abolished the inhibition caused by addition of the mucosal strip, indicating that mucosal gasotransmitters are the mediators of these effects. This suggests that the control of colonic motility exerted by the mucosa could fine tune the balance between transit and absorption. colon; bethanechol; nitric oxide; carbon monoxide; hydrogen sulfide; gasotransmitters THE TWO MAIN FUNCTIONS OF the colonic mucosa are: water and electrolyte absorption and barrier function, which is the basis of the defense against luminal pathogens and toxins. The epithelial layer of the colon consists of a single sheet of columnar epithelial cells folded into finger-like invaginations called Lieberkühn's crypts that contain four epithelial cell lineages: enterocytes, goblet cells, endocrine cells, and Paneth cells. In addition, there are multipotent stem cells located at the bottom of the crypts that differentiate into one of the epithelial cell types of the crypt wall collaborating in the physiological renewal of the mucosa (23). The epithelium maintains its selective barrier function through the formation of complex protein-protein networks that mechanically link adjacent cells and seal the intercellular space (5

Hydrogen sulphide as a signalling molecule regulating physiopathological processes in gastrointestinal motility

“…An excellent work using haem oxygenase‐2‐KO (Sha et al , ) and CSE KO mice (Sha et al , ) demonstrated that the transwall gradient is probably due to CO and potentiated by H 2 S. Both NO and CO are possibly released by SMP neurons. CO and H 2 S produced by the mucosa itself might also contribute to inhibit motility in the circular layer (Martin‐Cano et al , ). The consequence of this organization is that SMCs near the SMP are considerably more hyperpolarized than the cells near the MP and have the ability to oscillate at a frequency paced by ICC‐SMP (Mane et al , ).…”

Carbon monoxide contributes to the constipating effects of granisetron in rat colon

“…This contractile response is indicative of a nervous reflex that is abolished by tetrodotoxin and reduced by atropine and tackykinin antagonists[26]. Activation of enteric nerves by EFS mimics the in vivo conditions in which neurotransmitters are released by motor neurons to the neuroeffector apparatus; the interaction between the interstitial cells of Cajal, neurons, glial cells and smooth muscle cells generates contraction[27,28]. …”