B A Patel1. 1. School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK.
Abstract
BACKGROUND: Many studies have shown that mucosal serotonin (5-HT) is associated with motility, however, recently there have been some questions to the precise role of this transmitter. The majority of studies have focused on understanding the role of mucosal 5-HT on colonic migratory motor complexes, but very few studies have been carried out to understand how 5-HT release may be associated with other motility patterns. METHODS: Using distal colon segments from C57BL/6J mice, mucosal 5-HT overflow was monitored using amperometry while applying tension in longitudinal or circular directions to stretch the tissue. KEY RESULTS: Phasic and basal 5-HT levels were not associated with the strength of phasic contractions, while being altered using scopolamine and L-NNA. There was a significant increase in mucosal 5-HT with longitudinal and circular muscle stretch. A greater applied force was needed to activate 5-HT release in the circular muscle. In the longitudinal muscle, 5-HT levels increased with stretch until 3 mN, after which the levels returned back to baseline. This stretch-evoked 5-HT overflow was inhibited by transient receptor potential A1 (TRPA1) agonist, 30 μM ruthenium red in both circular and longitudinal muscle preparations. The decreased 5-HT overflow after 3 mN of tension was reversed using a 5-HT4 antagonist 100 nM GR113808. CONCLUSIONS & INFERENCES: Our findings show a relationship between colonic stretch and mucosal 5-HT overflow, while no relationship is observed with phasic colonic contractions. Such findings provide more insight into the role of mucosal 5-HT in influencing the pattern of colonic motility to diversify fecal propulsion.
BACKGROUND: Many studies have shown that mucosal serotonin (5-HT) is associated with motility, however, recently there have been some questions to the precise role of this transmitter. The majority of studies have focused on understanding the role of mucosal 5-HT on colonic migratory motor complexes, but very few studies have been carried out to understand how 5-HT release may be associated with other motility patterns. METHODS: Using distal colon segments from C57BL/6J mice, mucosal 5-HT overflow was monitored using amperometry while applying tension in longitudinal or circular directions to stretch the tissue. KEY RESULTS: Phasic and basal 5-HT levels were not associated with the strength of phasic contractions, while being altered using scopolamine and L-NNA. There was a significant increase in mucosal 5-HT with longitudinal and circular muscle stretch. A greater applied force was needed to activate 5-HT release in the circular muscle. In the longitudinal muscle, 5-HT levels increased with stretch until 3 mN, after which the levels returned back to baseline. This stretch-evoked 5-HT overflow was inhibited by transient receptor potential A1 (TRPA1) agonist, 30 μM ruthenium red in both circular and longitudinal muscle preparations. The decreased 5-HT overflow after 3 mN of tension was reversed using a 5-HT4 antagonist 100 nM GR113808. CONCLUSIONS & INFERENCES: Our findings show a relationship between colonic stretch and mucosal 5-HT overflow, while no relationship is observed with phasic colonic contractions. Such findings provide more insight into the role of mucosal 5-HT in influencing the pattern of colonic motility to diversify fecal propulsion.