Secretin is a peptide hormone that regulates water homeostasis throughout
the body, and influences the environment of the duodenum by regulating secretions
in the stomach and pancreas. Secretin is produced in the S cells of the duodenum,
which are located in the intestinal glands. In humans, the secretin peptide
is encoded by the SCT gene. Secretin was the first hormone to be identified.
Secretin also helps regulate the pH of the duodenum by: inhibiting the
secretion of gastric acid from the parietal cells of the stomach; and
stimulating the production of bicarbonate from the centroacinar cells
and intercalated ducts of the pancreas. In 2007, secretin was discovered to play
a role in osmoregulation by acting on the hypothalamus, pituitary gland, and
kidney. Discovery
In 1902, William Bayliss and Ernest Starling were studying how the nervous
system controls the process of digestion. It was known that the
pancreas secreted digestive juices in response to the passage of food through
the pyloric sphincter into the duodenum. They discovered that this process was
not, in fact, governed by the nervous system. They determined that a substance
secreted by the intestinal lining stimulates the pancreas after being
transported via the bloodstream. They named this intestinal secretion
secretin. Secretin was the first such "chemical messenger" identified. This
type of substance is now called a hormone, a term coined by Bayliss in
1905. Structure
Secretin is initially synthesized as a 120 amino acid precursor protein known
as prosecretin. This precursor contains an N-terminal signal peptide, spacer,
secretin itself, and a 72-amino acid C-terminal peptide.
The mature secretin peptide is a linear peptide hormone, which is composed of 27
amino acids and has a molecular weight of 3055. A helix is formed in the amino
acids between positions 5 and 13. The amino acids sequences of secretin have
some similarities to that of glucagon, vasoactive intestinal peptide, and
gastric inhibitory peptide. Fourteen of 27 amino acids of secretin reside in the
same positions as in glucagon, 7 the same as in VIP, and 10 the same as in
GIP. Secretin also has an amidated
carboxyl-terminal amino acid which is valine. The sequence of amino acids in
secretin is Leu-Gln-Arg-Leu-Leu-Gln-Gly-Leu-Val–NH2.
Physiology = Production=
Secretin is synthesized in cytoplasmic secretory granules of S-cells, which are
found mainly in the mucosa of the duodenum, and in smaller numbers in the
jejunum of the small intestine. = Stimulus=
Secretin is released into circulation and/or intestinal lumen in response to
low duodenal pH that ranges between 2 and 4.5 depending on species. Also, the
secretion of secretin is increased by the products of protein digestion
bathing the mucosa of the upper small intestine.
The acidity is due to hydrochloric acid in the chyme that enters the duodenum
from the stomach via the pyloric sphincter. Secretin targets the
pancreas, which causes the organ to secrete a bicarbonate-rich fluid that
flows into the intestine. Bicarbonate is a base that neutralizes the acid, thus
establishing a pH favorable to the action of other digestive enzymes in the
small intestine and preventing acid burns. Other factors are involved in the
release of secretin such as bile salts and fatty acids, which result in
additional bicarbonates being added to the small intestine. Secretin release is
inhibited by H2 antagonists, which reduce gastric acid secretion. As a
result, if the pH in the duodenum increases above 4.5, secretin cannot be
released. = Function=
Secretin stimulates the release of a watery bicarbonate solution from the
pancreatic and bile duct epithelium. Pancreatic centroacinar cells have
secretin receptors in their plasma membrane. As secretin binds to these
receptors, it stimulates adenylate cyclase activity and converts ATP to
cyclic AMP. Cyclic AMP acts as second messenger in intracellular signal
transduction and leads to an increase in the release of watery bicarbonate. It is
known to promote the normal growth and maintenance of the pancreas.
Secretin increases water and bicarbonate secretion from duodenal Brunner's glands
to buffer the incoming protons of the acidic chyme. It also enhances the
effects of cholecystokinin to induce the secretion of digestive enzymes and bile
from pancreas and gallbladder, respectively.
It counteracts blood glucose concentration spikes by triggering
increased insulin release from pancreas, following oral glucose intake.
Although secretin releases gastrin from gastrinomas, it inhibits gastrin release
from the normal stomach. It reduces acid secretion by parietal cells of the
stomach. It does this through at least three mechanisms: 1) By stimulating
release of somatostatin, 2) By inhibiting release of gastrin in the
pyloric antrum, and 3) By direct downregulation of the parietal cell acid
secretory mechanics. This helps neutralize the pH of the digestive
products entering the duodenum from the stomach, as digestive enzymes from the
pancreas function optimally at slightly basic pH.
In addition, secretin stimulates pepsinogen secretion from chief cells,
which can help break down proteins in food digestion. It stimulates release of
glucagon, pancreatic polypeptide and somatostatin.
Uses Secretin has been widely used in medical
field especially in pancreatic functioning test because it increases
pancreatic secretions. Secretin is either injected or given through a tube
that is inserted through nose, stomach then duodenum. This test can provide
information about whether there are any abnormalities in the pancreas which can
include gastrinoma, pancreatitis or pancreatic cancer.
Secretin has been proposed as a possible treatment for autism based on a
hypothetical gut-brain connection; as yet there is no evidence to support it
as effective. Osmoregulation
Secretin modulates water and electrolyte transport in pancreatic duct cells,
liver cholangiocytes, and epididymis epithelial cells. It is found to play a
role in the vasopressin-independent regulation of renal water reabsorption.
Secretin is found in the magnocellular neurons of the paraventricular and
supraoptic nuclei of the hypothalamus and along the neurohypophysial tract to
neurohypophysis. During increased osmolality, it is released from the
posterior pituitary. In the hypothalamus, it activates vasopressin
release. It is also needed to carry out the central effects of angiotensin II.
In the absence of secretin or its receptor in the gene knockout animals,
central injection of angiotensin II was unable to stimulate water intake and
vasopressin release. It has been suggested that abnormalities
in such secretin release could explain the abnormalities underlying type D
syndrome of inappropriate antidiuretic hormone hypersecretion. In these
individuals, vasopressin release and response are normal, although abnormal
renal expression, translocation of aquaporin 2, or both are found. It has
been suggested that "Secretin as a neurosecretory hormone from the
posterior pituitary, therefore, could be the long-sought vasopressin independent
mechanism to solve the riddle that has puzzled clinicians and physiologists for
decades." Food intake
Secretin and its receptor are found in discrete nuclei of the hypothalamus,
including the paraventricular nucleus and the arcuate nucleus, which are the
primary brain sites for regulating body energy homeostasis. It was found that
both central and peripheral injection of Sct reduce food intake in mouse,
indicating an anorectic role of the peptide. This function of the peptide is
mediated by the central melanocortin system.
See also Secretin family
Secretin receptor References
Further reading External links
Overview at colostate.edu Secretin at the US National Library of
Medicine Medical Subject Headings Physiology: 6s6ch2_17 - Essentials of
Human Physiology