CrossTalk proposal: 5-HT is necessary for peristalsis.

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