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Serotonin and neuroprotection in functional bowel disorders
Author(s) -
Gershon M. D.,
Liu M.t.
Publication year - 2007
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2007.00962.x
Subject(s) - tegaserod , neuroprotection , enteric nervous system , receptor , agonist , irritable bowel syndrome , pharmacology , interstitial cell of cajal , neurite , medicine , endocrinology , serotonin , partial agonist , receptor antagonist , gastrointestinal function , neuroscience , biology , antagonist , biochemistry , smooth muscle , in vitro
The 5‐HT 4 partial agonist tegaserod is effective in the treatment of chronic constipation and constipation predominant irritable bowel syndrome. 5‐HT 4 receptors are located on presynaptic terminals in the enteric nervous system. Stimulation of 5‐HT 4 receptors enhances the release of acetylcholine and calcitonin gene related peptide from stimulated nerve terminals. This action strengthens neurotransmission in prokinetic pathways, enhancing gastrointestinal motility. The knockout of 5‐HT 4 receptors in mice not only slows gastrointestinal activity but also, after 1 month of age, increases the age‐related loss of enteric neurons and decreases the size of neurons that survive. 5‐HT 4 receptor agonists, tegaserod and RS67506, increase numbers of enteric neurons developing from precursor cells and/or surviving in culture; they also increase neurite outgrowth and decrease apoptosis. The 5‐HT 4 receptor antagonist, GR113808, blocks all of these effects, which are thus specific and 5‐HT 4 ‐mediated. 5‐HT 4 receptor agonists, therefore, are neuroprotective and neurotrophic for enteric neurons. Because the age‐related decline in numbers of enteric neurons may contribute to the dysmotilities of the elderly, the possibility that the neuroprotective actions of 5‐HT agonists can be utilized to prevent the occurrence or worsening of these conditions should be investigated.