Gastrointestinal System :: Signalling Molecules

Gastrointestinal System :: Hormones, Paracrines, & Transmitters

Ligand	Source	Stimulus	Action
Gastrin [multiple cleavage forms, all with the same four bioactive C-terminal amino acids]	mostly G-cells in the stomach antrum; there are a few duodenal and pancreatic G-cells	GRP (gastrin releasing polypeptide) from vagal postganglionics; stomach antral luminal products of protein digestion	via CCK-B receptor, it stimulates ECL (enterochromaffin-like) cells to secrete histamine and parietal cells to secrete HCl promotes growth of the gastric mucosa stimulates gastric motility constricts the LES
Cholecystokinin (CCK) [also known as pancreozymin (PZ); exists in multiple forms; tyrosine near the C-terminus is sulfated; has the same four C-terminal amino acids as gastrin ]	I-cells in the proximal small intestine; some nerve endings in the ileum and cecum	luminal peptides, amino acids, and fatty acids	via CCK-A receptor, it causes gallbladder contraction ↑ exocrine secretions of the pancreatic acinar cells inhibits gastric emptying enhances motility of the small bowel and colon via CCK-B receptor, it may compete with gastrin and inhibit acid secretion
Secretin [a 27-aa polypeptide]	duodenal S-cells	intestinal luminal contents with a pH < 4.5	inhibits gastric acid secretion, probably through D-cells stimulates pancreatic secretion of NaHCO₃⁻ from pancreatic ductal cells
Vasoactive intestinal peptide (VIP) [a 28-aa polypeptide of the secretin family]	as a neurotransmitter or neurohormone from nerve endings	parasympathetic nerve stimulation	relaxes smooth muscle in the LES and salivary gland arterioles stimulates intestinal secretion of electrolytes
Histamine	ECL cells in the fundus and body of the stomach	acetylcholine; gastrin	most potent activator of parietal cell acid secretion
Somatostatin	D-cells in the stomach antrum; also found in the pancreas	acidic gastric chyme (pH < 3)	inhibits gastrin secretion inhibits the secretion of VIP, GIP, secretin, motilin, and pancreatic exocrine secretions
Gastrin releasing polypeptide (GRP) [also known as Bombesin; a 27-aa polypeptide]	postganglionic parasympathetic nerve terminals innervating G-cells	vagal stimulation; stomach distension leading to long reflexes	stimulates gastrin release
Gastric inhibitory peptide (GIP) [also known as glucose-dependent insulinotropic polypeptide; a 42-aa polypeptide of the secretin family]	K-cells in the proximal small bowel	glucose and fatty acids in duodenal chyme	promotes insulin secretion (incretin effect) ↓ gastric acid secretion (possible D-cell agonist) decreases gastric motility
Motilin [a 22 aa polypeptide]	small bowel	unknown; it is released during the interdigestive period at about 100 minute intervals	likely to initiate the migrating motility complex, the GI “housekeeping” contractions
Peptide YY [a 36-aa polypeptide]	throughout the gut, mainly in the distal segments, from intestinal L-cells	nutrients in meat	inhibits food intake inhibits gastric acid secretion and gastric motility
Glucagon-like peptide-1 (GLP-1) [a 37-aa polypeptide of the secretin family]	intestine	glucose and fatty acids	promotes insulin secretion (incretin effect) inhibits glucagon secretion, gastric emptying, and food intake degraded by dipeptidyl peptidase-4 (DPP-4)
Ghrelin [a 28-aa polypeptide]	epithelial cells in the stomach fundus	food related: rises during fasting, drops with feeding	increases hunger stimulates gastric emptying stimulates GH secretion
Guanylin [a 15-aa polypeptide]	goblet cells throughout the GI tract, but largely in the distal ileum and proximal colon	cholinergic stimulation	acts on the luminal border, binding to a transmembrane receptor with guanylyl cyclase activity, resulting in ↑ cAMP, and causing intestinal Cl⁻ secretion and inhibition of intestinal fluid absorption
Neurotensin [a 13-aa polypeptide]	ileal mucosa	fatty acids	inhibits intestinal motility ↑ ileal blood flow
Oxyntomodulin [a 37-aa polypeptide]	L-cells	food intake in proportion to caloric intake	inhibits gastric secretion and motility acts as a satiety signal

Ligand

Source

Stimulus

Action

Gastrin [multiple cleavage forms, all with the same four bioactive C-terminal amino acids]

mostly G-cells in the stomach antrum; there are a few duodenal and pancreatic G-cells

GRP (gastrin releasing polypeptide) from vagal postganglionics; stomach antral luminal products of protein digestion

via CCK-B receptor, it stimulates ECL (enterochromaffin-like) cells to secrete histamine and parietal cells to secrete HCl
promotes growth of the gastric mucosa
stimulates gastric motility
constricts the LES

Cholecystokinin (CCK) [also known as pancreozymin (PZ); exists in multiple forms; tyrosine near the C-terminus is sulfated; has the same four C-terminal amino acids as gastrin ]

I-cells in the proximal small intestine; some nerve endings in the ileum and cecum

luminal peptides, amino acids, and fatty acids

via CCK-A receptor, it causes gallbladder contraction
↑ exocrine secretions of the pancreatic acinar cells
inhibits gastric emptying
enhances motility of the small bowel and colon
via CCK-B receptor, it may compete with gastrin and inhibit acid secretion

Secretin [a 27-aa polypeptide]

duodenal S-cells

intestinal luminal contents with a pH < 4.5

inhibits gastric acid secretion, probably through D-cells
stimulates pancreatic secretion of NaHCO₃⁻ from pancreatic ductal cells

Vasoactive intestinal peptide (VIP) [a 28-aa polypeptide of the secretin family]

as a neurotransmitter or neurohormone from nerve endings

parasympathetic nerve stimulation

relaxes smooth muscle in the LES and salivary gland arterioles
stimulates intestinal secretion of electrolytes

Histamine

ECL cells in the fundus and body of the stomach

acetylcholine; gastrin

most potent activator of parietal cell acid secretion

Somatostatin

D-cells in the stomach antrum; also found in the pancreas

acidic gastric chyme (pH < 3)

inhibits gastrin secretion
inhibits the secretion of VIP, GIP, secretin, motilin, and pancreatic exocrine secretions

Gastrin releasing polypeptide (GRP) [also known as Bombesin; a 27-aa polypeptide]

postganglionic parasympathetic nerve terminals innervating G-cells

vagal stimulation;
stomach distension leading to long reflexes

stimulates gastrin release

Gastric inhibitory peptide (GIP) [also known as glucose-dependent insulinotropic polypeptide; a 42-aa polypeptide of the secretin family]

K-cells in the proximal small bowel

glucose and fatty acids in duodenal chyme

promotes insulin secretion (incretin effect)
↓ gastric acid secretion (possible D-cell agonist)
decreases gastric motility

Motilin [a 22 aa polypeptide]

small bowel

unknown; it is released during the interdigestive period at about 100 minute intervals

likely to initiate the migrating motility complex, the GI “housekeeping” contractions

Peptide YY [a 36-aa polypeptide]

throughout the gut, mainly in the distal segments, from intestinal L-cells

nutrients in meat

inhibits food intake
inhibits gastric acid secretion and gastric motility

Glucagon-like peptide-1 (GLP-1) [a 37-aa polypeptide of the secretin family]

intestine

glucose and fatty acids

promotes insulin secretion (incretin effect)
inhibits glucagon secretion, gastric emptying, and food intake
degraded by dipeptidyl peptidase-4 (DPP-4)

Ghrelin [a 28-aa polypeptide]

epithelial cells in the stomach fundus

food related:
rises during fasting, drops with feeding

increases hunger
stimulates gastric emptying
stimulates GH secretion

Guanylin [a 15-aa polypeptide]

goblet cells throughout the GI tract, but largely in the distal ileum and proximal colon

cholinergic stimulation

acts on the luminal border, binding to a transmembrane receptor with guanylyl cyclase activity, resulting in ↑ cAMP, and causing intestinal Cl⁻ secretion and inhibition of intestinal fluid absorption

Neurotensin [a 13-aa polypeptide]

ileal mucosa

fatty acids

inhibits intestinal motility
↑ ileal blood flow

Oxyntomodulin [a 37-aa polypeptide]

L-cells

food intake in proportion to caloric intake

inhibits gastric secretion and motility
acts as a satiety signal