Secretin is a
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
that regulates
water homeostasis throughout the body and influences the environment of the
duodenum by regulating secretions in the
stomach,
pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an ...
, and
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
. It is a
peptide hormone 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
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Secretin helps regulate the
pH of the duodenum by (1) inhibiting the secretion of
gastric acid from the
parietal cells of the stomach and (2) stimulating the production of
bicarbonate
In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula .
Bicarbonate serves a crucial biochemi ...
from the ductal cells of the pancreas.
It also stimulates the secretion of bicarbonate and water by
cholangiocytes in the bile duct, protecting it from
bile acids
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts.
Primar ...
by controlling the pH and promoting the flow in the duct.
Meanwhile, in concert with secretin's actions, the other main hormone simultaneously issued by the duodenum,
cholecystokinin (CCK), is stimulating the
gallbladder to contract, delivering its stored bile.
Prosecretin is a precursor to secretin, which is present in digestion. Secretin is stored in this unusable form, and is activated by
gastric acid. This indirectly results in the neutralisation of duodenal pH, thus ensuring no damage is done to the small intestine by the aforementioned acid.
In 2007, secretin was discovered to play a role in
osmoregulation by acting on the
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...
,
pituitary gland
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The h ...
, and
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
.
History
Secretin was the first hormone to be identified. In 1902,
William Bayliss
Sir William Maddock Bayliss (2 May 1860 – 27 August 1924) was an English physiologist.
Life
He was born in Wednesbury, Staffordshire but shortly thereafter his father, a successful merchant of ornamental ironwork, moved his family to a ...
and
Ernest Starling
Ernest Henry Starling (17 April 1866 – 2 May 1927) was a British physiologist who contributed many fundamental ideas to this subject. These ideas were important parts of the British contribution to physiology, which at that time led the world ...
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 (chyme) through the pyloric sphincter into the duodenum. They discovered (by cutting all the nerves to the pancreas in their experimental animals) 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 hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
, a term coined by Starling 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 (residues 28–54), 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
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bio ...
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 (VIP), and
gastric inhibitory peptide (GIP). 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
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain ( protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
amino acid which is valine.
The sequence of amino acids in secretin is H–
His-
Ser-
Asp-
Gly-
Thr-
Phe-
Thr-
Ser-
Glu-
Leu
Leu may refer to:
Businesses and organisations
* LEU, NYSE American stock symbol for Centrus Energy Corp.
* London Ecology Unit, a former body (1986-2000) which advised London boroughs on environmental matters
* Free and Equal (''LeU - Liberi e ...
-
Ser-
Arg-
Leu
Leu may refer to:
Businesses and organisations
* LEU, NYSE American stock symbol for Centrus Energy Corp.
* London Ecology Unit, a former body (1986-2000) which advised London boroughs on environmental matters
* Free and Equal (''LeU - Liberi e ...
-
Arg-
Asp-
Ser-
Ala-
Arg-
Leu
Leu may refer to:
Businesses and organisations
* LEU, NYSE American stock symbol for Centrus Energy Corp.
* London Ecology Unit, a former body (1986-2000) which advised London boroughs on environmental matters
* Free and Equal (''LeU - Liberi e ...
-
Gln
Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...
-
Arg-
Leu
Leu may refer to:
Businesses and organisations
* LEU, NYSE American stock symbol for Centrus Energy Corp.
* London Ecology Unit, a former body (1986-2000) which advised London boroughs on environmental matters
* Free and Equal (''LeU - Liberi e ...
-
Leu
Leu may refer to:
Businesses and organisations
* LEU, NYSE American stock symbol for Centrus Energy Corp.
* London Ecology Unit, a former body (1986-2000) which advised London boroughs on environmental matters
* Free and Equal (''LeU - Liberi e ...
-
Gln
Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...
-
Gly-
Leu
Leu may refer to:
Businesses and organisations
* LEU, NYSE American stock symbol for Centrus Energy Corp.
* London Ecology Unit, a former body (1986-2000) which advised London boroughs on environmental matters
* Free and Equal (''LeU - Liberi e ...
-
Val
Val may refer to: Val-a
Film
* ''Val'' (film), an American documentary about Val Kilmer, directed by Leo Scott and Ting Poo
Military equipment
* Aichi D3A, a Japanese World War II dive bomber codenamed "Val" by the Allies
* AS Val, a Sov ...
–NH
2.
Physiology
Production and secretion
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.
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; the acidity is due to
hydrochloric acid
Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the dige ...
in the
chyme that enters the duodenum from the stomach via the
pyloric sphincter.
Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper 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
pH regulation
Secretin primarily functions to neutralize the pH in the
duodenum, allowing digestive
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s from the pancreas (e.g.,
pancreatic amylase and
pancreatic lipase) to function optimally.
Secretin targets the
pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an ...
; 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 adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal tra ...
.
Cyclic AMP acts as second messenger in intracellular signal transduction and causes the organ to secrete a
bicarbonate
In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula .
Bicarbonate serves a crucial biochemi ...
-rich fluid that flows into the
intestine
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans an ...
. Bicarbonate is a base that neutralizes the acid, thus establishing a pH favorable to the action of other digestive enzymes in the small intestine.
Secretin also increases water and bicarbonate secretion from duodenal
Brunner's gland
Brunner's glands (or duodenal glands) are compound tubular submucosal glands found in that portion of the duodenum which is above the hepatopancreatic sphincter (i.e sphincter of Oddi). It also contains submucosa which creates special glands. ...
s to buffer the incoming
protons
A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron m ...
of the acidic chyme,
and also 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
In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pr ...
of the parietal cell acid secretory mechanics.
It counteracts
blood glucose
Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the b ...
concentration spikes by triggering increased
insulin release from pancreas, following oral
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
intake.
Osmoregulation
Secretin modulates
water
Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as ...
and
electrolyte transport in
pancreatic duct cells,
liver
cholangiocytes
Cholangiocytes are the epithelial cells of the bile duct. They are cuboidal epithelium in the small interlobular bile ducts, but become columnar and HCO3:-secreting in larger bile ducts approaching the porta hepatis and the extrahepatic ducts. Th ...
,
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
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. 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 (SIADH).
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
The arcuate nucleus of the hypothalamus (also known as ARH, ARC, or infundibular nucleus) is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes seve ...
, 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.
Uses
Secretin is used in a diagnostic tests for pancreatic function; secretin is injected and the pancreatic output can then be imaged with
magnetic resonance imaging, a noninvasive procedure, or secretions generated as a result can gathered either through an endoscope or through tubes inserted through the mouth, down into the duodenum.
A recombinant human secretin has been available since 2004 for these diagnostic purposes.
There were problems with the availability of this agent from 2012 to 2015.
Research
A wave of enthusiasm for secretin as a possible treatment for
autism arose in the 1990s based on a hypothetical gut-brain connection; as a result the NIH ran a series of clinical trials that showed that secretin was not effective, which brought an end to popular interest.
A high-affinity and optimized secretin receptor antagonist (Y10,c
16,K20I17,Cha22,R25)sec(6-27) has been designed and developed which has allowed the structural characterization of secreting inactive conformation.
See also
*
Secretin family
*
Secretin receptor
References
Further reading
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External links
Overview at colostate.edu*
*
{{Gastrointestinal hormones
Peptide hormones
Intestinal hormones
Digestive system
Treatment of autism
1902 in biology