5-Hydroxytryptamine4 receptor agonists and colonic motility

Abstract

5-Hydroxytryptamine (5-HT) released from enterochromaffin cells regulates gastrointestinal function in either an excitatory or inhibitory manner. 5-HT3 and 5-HT4 receptors in the gut have been the focus of clinical studies on the management of gastrointestinal motility disorders. 5-HT stimulates intestinal propulsive reflexes through 5-HT4 receptors. 5-HT4 receptor agonists can stimulate upper or lower gut motility, depending on their selectivity and affinity. In the guinea pig colon, the distribution of 5-HT4 receptors in the myenteric plexus and circular muscle layer differs between the proximal and distal regions. 5-HT stimulates intestinal motility via excitatory neurons while causing relaxation of the circular muscle via 5-HT4 receptors. In the light of these findings on the distribution of 5-HT4 receptors, the effects of receptor agonist compounds could vary depending on the species of experimental animal and the anatomical region studied.

Chronic Constipation: An Evidence-Based Review

“…4 ) receptors are found in the primary afferent neurons, smooth muscle cells, enterochromaffin cells, and the myenteric plexus of the colon. 155 They mediate the release of other neurotransmitters that initiate peristaltic action in the bowel. 155,156 Tegaserod, a 5-HT 4 partial agonist, was approved by the FDA for use in 2002 both for constipation the dominant type of irritable bowel syndrome and also for idiopathic constipation in patients under the age of 65 years.…”

“…155 They mediate the release of other neurotransmitters that initiate peristaltic action in the bowel. 155,156 Tegaserod, a 5-HT 4 partial agonist, was approved by the FDA for use in 2002 both for constipation the dominant type of irritable bowel syndrome and also for idiopathic constipation in patients under the age of 65 years. Despite its efficacy shown by multiple randomized, placebo-controlled, clinical trials from different countries, [121][122][123][124] the FDA disapproved marketing of tegaserod in 2007 because of a small increased risk in cardiovascular events, which led to its final withdrawal in 2008.…”

Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine–induced Parkinson's disease rats

“…5 According to in vitro and in vivo studies, 5-HT regulates GI motility, mostly via the 5-HT 4 and 5-HT 3 receptors. [6][7][8][9] Significant alterations of the monoamine system are observed in the GI tract of the elderly and patients with advanced Parkinson's disease (PD), accompanied with GI dysfunction. 10,11 D 2 receptor antagonists are used as prokinetic drugs in the GI tract.…”

Distribution of 5-HT3, 5-HT4, and 5-HT7Receptors Along the Human Colon

“…41 Serotonin receptors for instance are widespread throughout the gastrointestinal tract in small animal models and humans but the proportion and type of receptors at particular regions are different. [41][42][43] In addition, human 5-HT receptors are considerably different in their composition as evident by the diverse splice variants in 5-HT 4 and 5-HT 7 receptors and the additional 5-HT 3 receptor subunits. 1,19,44 The function and pharmacological responses of 5-HT receptors in the intestine also varies between small animal models and humans 15,41,45,46 and therefore this study was undertaken to gain an insight to the distribution of 5-HT 3 , 5-HT 4 , and 5-HT 7 receptors expressed in the human ileum and throughout the human colon.…”