Abstract
The overwhelming preponderance of the 5-HT of every known mammal is in the gut (Erspamer, 1966; Gershon & Tack, 2007; Gershon, 2013). Enteric 5-HT must be an important signalling molecule to be so conserved. Most enteric 5-HT is in enterochromaffin (EC) cells, but smaller amounts are present in myenteric neurons. Despite their small numbers, serotonergic neurons project widely throughout the enteric nervous system (ENS) and also innervate interstitial cells of Cajal (ICC) (Okamoto et al. 2014). The abundance and variety of enteric 5-HT receptors (5-HT1-7 and subtypes) also suggest that 5-HT plays a significant role in GI physiology (Smith et al. 2014). The efficacy of therapies targeting enteric 5-HT or its receptors against GI motility disorders supports this idea (Gershon & Tack, 2007; Gershon, 2013). Beyond motility and secretion, putative roles that 5-HT plays include metabolism, osteogenesis, immunity, neurogenesis and neuroprotection (Gershon, 2013). The multiplicity of enteric 5-HT targets and receptors complicates ascertaining the physiological roles of 5-HT. Controversy is thus to be expected and has appeared in recent papers, which question whether EC or neuronal 5-HT has anything to do with peristalsis (Keating & Spencer, 2010; Spencer et al. 2011; Sia et al. 2013; Spencer et al. 2013). These papers are important not because enteric 5-HT is vestigial (it is not) or that its roles in normal and abnormal GI motility can be ignored (they cannot). Instead, they highlight common misunderstandings about peristaltic reflexes and 5-HT cellular biology. The papers focus on colonic migrating motor complexes (CMMCs), which are aborally propagating propulsive contractile complexes, essentially peristaltic reflexes. The authors assert that they can evoke CMMCs after mucosal removal or depleting 5-HT with reserpine; therefore, they conclude that neither EC cells, nor neuronal 5-HT is necessary for CMMCs. To comprehend what is misunderstood, it is necessary to discuss basic information about 5-HT and GI motility.
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