Download Hormones of the Gut

Hormones of the Gut
I. Beginning of Endocrinology
A. Bayliss and Starling--1902
1. Acidification of denervated duodenum or jejunum
stimulated pancreatic exocrine secretion.
2. Injected extract of jejunal mucosa also stimulated
pancreatic exocrine secretion.
3. Postulated a humoral regulatory factor they called
“Secretin.”
B. Secretin finally isolated in 1961.
II. Gut Regulatory Peptides
A. Gut Nervous System
B. Endocrine cells of mucosa
1. Basal secretory granules
C. Gut Peptides may be
1. Hormones
a) Travel to different organ through blood stream.
2. Paracrine
3. Neurosecretory
4. Neurotransmitters
III. Secretin
A. 29 amino acid peptide
1. Related to: glucagon, GIP, VIP, PHI, PHM (Secretin
family)
B. Action:
1. Stimulates Bicarbonate and Water Secretion by
Pancreas
C. Secretin Control
IV. Gastrin
A. 1905, Edkins discovered that an extract of gastric
mucosa stimulated acid secretion that he called
Gastrin.
B. 1960s, Gregory isolated and sequenced Gastrin.
C. 3 biologically active forms:
1. “Big” = 34 amino acids
2. ‘Little” = 17 amino acids
3. “Mini” = 14 amino acids
4. Structurally similar to Cholecystokinin:
a) Gastrin-Cholecystokinin Family.
D. Found in endocrine cells of gastric antrum.
1. Also identified in CNS.
E. Stimulated by proteins and amino acids in gastric
lumen.
1. Carbohydrates and Fats in effective.
2. Somatostatin inhibits Gastrin release
F. Gastrin Action
1. Stimulates Acid Secretion by Gastric Mucosa
a) May be due to stimulation of histamine release by
neighboring cells (paracrine)
2. Stimulates growth of parietal cells of the Gastric
Mucosa
3. Stimulates Mucosal blood flow
4. Stimulates Pepsin Release
G. Gastrin Control
V. Cholecystokinin (CCK)
A. History
1. 1928: Fat in small intestine stimulates the gall
bladder to contract--cholecystokinin.
2. 1940s: Extract of duodenal mucosa stimulates
pancreas to secrete enzymes--pancreozymin.
3. 1964-8: Purification of a single substance that
stimulated both contraction of the gall bladder and
pancreatic enzyme secretion--settled on one name:
cholecystokinin (CCK).
B. Structure
1. Polypeptide found in different forms including: 58,
39, 33, & 8 amino acids.
2. 8 amino acid form has full biological potency.
3. Carboxy terminal 8 amino acids identical in all
forms.
4. Larger forms may be prohormones.
5. Preprocholecystokinin found: 115 amino acids.
C. Cholecystokinin Location:
1. Located in duodenal and proximal jejunal mucosa.
2. Also found in CNS.
D. CCK Secretion Stimulated
1. By the presence of intraduodenal protein or fat.
2. May be a low molecular weight
CCK-releasing factor.
3. Release is inhibited by somatostatin.
E. CCK Actions
1. Stimulates contraction of gall bladder, forcing bile
into the duodenum.
2. Stimulates pancreatic enzyme secretion.
3. Trophic effects on pancreatic acini.
4. Causes sphincter of Oddi to relax.
5. Induces satiety.
F. CCK Control
VI. Somatostatin
A. 14 & 28 amino acid forms.
B. Found in hypothalamus, throughout CNS and Gut
(including pancreas)
C. Major inhibitory peptide of Gut. Inhibits
secretion of
1. insulin
2. glucagon
3. CCK
4. secretin
5. gastrin
6. VIP
7. somatostatin (autocrine)
D. Somatostatin Control
VII.
Other Peptides
A. Vasoactive Intestinal Peptide (VIP)
1. Neurotransmitter/neuroendocrine
2. Relax esophageal and anal sphincter
3. Increases blood flow in the gut
4. Causes penile erection
B. Gastrin-Releasing Peptide (GRP)
1. Neurotransmitter/neuroendocrine
2. Stimulates release of Gastrin
C. Substance P
1. Neurotransmitter
2. Stimulates Contraction of Smooth Muscle
D. Enkephalins
E. Neurotransmitter
F. Inhibits gut motility, antagonizes action of
Substance P