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ACh: acetylcholine

ANS: autonomic nervous system

AQP: aquaporin

CA: carbonic anhydrase

CCK: cholecystokinin

CFTR: cystic fibrosis transmembrane conductance regulator

CTZ: chemoreceptor trigger zone

CYP: cytochrome P450

DOR: delta opioid receptor

DRA: downregulated in adenoma

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

HERG: human ether-a-go-go related gene

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

NSAID: nonsteroidal anti-inflammatory drug

OTC: over the counter

PACAP: pituitary adenylyl cyclase–activating peptide

PAF: platelet-activating factor

PEG: polyethylene glycol

QT: ECG interval

SERT: serotonin transporter

SGLT: sodium-glucose cotransporter

SLC: solute carrier transporter

SSRI: selective serotonin reuptake inhibitor

SST: somatostatin

STN: solitary tract nucleus

TJ: tight junction

TMEM: transmembrane protein

USP: U.S. Pharmacopeia

VIP: vasoactive intestinal peptide


The 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), and local and circulating hormones. Of these, perhaps the most important regulator of physiological gut function is the ENS (Figure 50–1) (Furness, 2006; Furness, 2012; Grundy et al., 2006).

Figure 50–1

The neuronal network that initiates and generates the peristaltic response. Mucosal stimulation leads to release of serotonin by enterochromaffin cells (8), which excites the intrinsic primary afferent neurons (1), which then communicate with ascending (2) and descending (3) interneurons in the local reflex pathways. The reflex results in contraction at the oral end via the excitatory motor neuron (6) and aboral relaxation via the inhibitory motor neuron (5). The migratory myoelectric complex (see text) is shown here as being conducted by a different chain of interneurons (4). Another intrinsic primary afferent neuron with its cell body in the submucosa also is shown (7). MP, myenteric plexus; CM, circular muscle; LM, longitudinal muscle; SM, submucosa; Muc, mucosa. (Adapted with permission from Kunze WA, Furness JB. The enteric nervous system and regulation of intestinal motility. Annu Rev Physiol, 1999, 61:117–142. Permission conveyed via Copyright Clearance Center, Inc.)

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 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 ...

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