Chromatographic analysis of age-related changes in mucosal serotonin transmission in the murine distal ileum

Abstract

BackgroundIn the upper bowel, alterations in motility and absorption of key nutrients have been observed as part of the normal ageing process. Serotonin (5-HT) is a key signalling molecule in the gastrointestinal tract and is known to influence motility, however little is known of how the ageing process alters 5-HT signalling processes in the bowel.ResultsAn isocratic chromatographic method was able to detect all 5-HT precursors and metabolites. Using extracellular and intracellular sampling approaches, we were able to monitor all key parameters associated with the transmission process. There was no alteration in the levels of tryptophan and 5-HTP between 3 and 18 month old animals. There was a significant increase in the ratio of 5-HT:5-HTP and an increase in intracellular 5-HT between 3 and 18 month old animals suggesting an increase in 5-HT synthesis. There was also a significant increase in extracellular 5-HT with age, suggesting increased 5-HT release. There was an age-related decrease in the ratio of intracellular 5-HIAA:extracellular 5-HT, whilst the amount of 5-HIAA did not change with age. In the presence of an increase in extracellular 5-HT, the lack of an age-related change in 5-HIAA is suggestive of a decrease in re-uptake via the serotonin transporter (SERT).ConclusionsWe have used intracellular and extracellular sampling to provide more insight into alterations in the neurotransmission process of 5-HT during normal ageing. We observed elevated 5-HT synthesis and release and a possible decrease in the activity of SERT. Taken together these changes lead to increased 5-HT availability and may alter motility function and could lead to the changes in adsorption observed in the elderly.

Dietary Lipid Modulation of Intestinal Serotonin in Ballan Wrasse (Labrus bergylta)—In Vitro Analyses

“…Recent investigations in humans and mice have identified specific chemosensory receptors in EC cells such as TRPA1 (Transient Receptor Potential Cation Channel Subfamily A Member 1), ADRA2A (Adrenoceptor Alpha 2A) and TRPC4 (Transient Receptor Potential Cation Channel Subfamily C Member 4) that stimulate the production and release of 5-HT from the cytoplasm to the gut mucosa (19)(20)(21). Serotonin is then bound to specific receptors of intrinsic primary afferent neurons (IPANs) which activate a cascade of interneurons and motor neurons within the enteric circuitry causing changes in the motility of the GI tract (15). Remaining 5-HT in the pre-synaptic space of the mucosa is then transported into epithelial cells via the serotonin transporter (Solute Carrier Family 6 Member 4 -SLC6A4) and metabolized by monoamine oxidase (MAO) (2,13).…”

“…Biosynthesis of 5-HT requires the conversion of the essential amino acid tryptophan to 5-hydroxytryptophan (5-HTP) by the rate limiting enzyme tryptophan hydrolase (TPH) ( 13 , 14 ) and the non-rate limiting enzyme dopa decarboxylase (DDC). Mammals and some other higher vertebrates present two TPH isoforms; TPH1 which is found in the intestinal EC cells and TPH2 uniquely found in serotonergic neurons in both the brain and the intestine ( 13 , 15 ). Both Tph1 and Tph2 have been characterized in fish, some species have two isoforms of Tph1 ( 16 , 17 ).…”

Meeting report: British Society for Research on Ageing (BSRA) annual scientific meeting 2012, Aston University, Birmingham, 3rd to 4th July 2012

“…Fecal output is negatively affected by age and the percentage of compaction increases causing decreased colonic motility. These changes are suggested to be a result of reduced mucosal serotonin availability and a subsequent reduction in mucosal serotonin transporter (SERT) expression, which has been shown in aging [ 19 ]. Serotonin is the neurotransmitter responsible for nutrition absorption and motility in the GI tract.…”