++
Abbreviations
ACh: acetylcholine
ANS: autonomic nervous system
CCK: cholecystokinin
CFTR: cystic fibrosis transmembrane conductance regulator
CTZ: chemoreceptor trigger zone
CYP: cytochrome P450
DOR: delta opioid receptor
ECG: electrocardiogram
ENaC: epithelial sodium channel
ENS: enteric nervous system
FDA: U.S. Food and Drug Administration
GC: guanyl cyclase
GERD: gastroesophageal reflux disease
GI: gastrointestinal
GLP: glucagon-like peptide
GPCR: G protein-coupled receptor
HIV: human immunodeficiency virus
5HT: serotonin, 5-hydroxytryptamine
IBS: irritable bowel syndrome
KOR: kappa opioid receptor
MOR: mu opioid receptor
NEP: neutral endopeptidase
NHE: Na+-H+ exchanger
NK: neurokinin
NO: nitric oxide
NTS: nucleus of the solitary tract
OTC: over-the-counter
PEG: polyethylene glycol
Pgp: P-glycoprotein (MDR1, ABCB1)
PK: protein kinase (e.g., PKA, PKC)
PONV: postoperative nausea and vomiting
QT: ECG interval (duration of ventricular depolarization and repolarization)
SLC: solute carrier transporter
SSRI: selective serotonin reuptake inhibitor
SST: somatostatin
TMEM: transmembrane protein
USP: U.S. Pharmacopeia
VIP: vasoactive intestinal peptide
+++
GASTROINTESTINAL MOTILITY
++
The gastrointestinal (GI) tract is in a continuous contractile, absorptive, and secretory state. The control of this state is complex, with contributions by the muscle and epithelium, the enteric nervous system (ENS), the autonomic nervous system (ANS), microbial mediators, innate and adaptive immune cells and their mediators, and local enteroendocrine and circulating hormones. Of these, the master regulator of physiological gut function is the ENS (Figure 54–1) (Fung and Vanden Berghe, 2020; Furness, 2012; Sharkey et al., 2018; Spencer and Hu, 2020).
++++
The ENS is an extensive collection of nerves and glial cells that constitutes the third division of the ANS. It is the only part of the ANS that is truly capable of autonomous function if separated from the CNS. The ENS lies within the wall of the GI tract and is organized into two connected networks of neurons, nerve fibers, and glial cells: the myenteric (Auerbach) plexus, found between the circular and longitudinal muscle layers, and the submucosal (Meissner) plexus, located in the submucosa (Furness, 2012; Sharkey, 2015). The former is largely responsible for motor control, whereas the latter regulates secretion, ion and fluid transport, and blood ...