3. GI hormones: paracrine mediators, humoral regulation
*What are the parts of neural regulation (extrinsic and intrinsic parts)?
1. Extrinsic NS: somatic and autonomic = symp. and parasymp.
2. Intrinsic NS: enteric NS
What is the autonomic nervous system (ANS) divided into, and which are more important?
***3. ENS (effects are independent of higher centers)
***What parts of the GI system does the vagus nerve innervate?
esophagus, stomach, gallbladder, pancreas, 1st part of SI and proximal colon
***What does the vagus nerve do in the gut?
sensory nerve. Transmit info from gut to brain about glucose, pH, osmolality, mechanical stimuli (level of stretch). Signals are transmitted by afferent fibers to brain and then back to gut all through vagus nerve. (vagovagal reflex)
***What neurotransmitter is present in the parasymp. dividsion?
***What are characteristics and functions of the pelvic nerve?
Impulses originate in 2nd, 3rd, and 4th sacral segments of spinal cord. Innervates descending colon, sigmoid colon, rectum and anal regions. Function in defecation reflex
What are characteristics and functions of symp. division?
1. Spinal cord T1-L3
2. Stimulates most, if not all, areas of gut
3. Decrease in activity of GI tract: decrease motor and secretory functions: direct effect of norepinephrine on SM and on neurons of enteric nervous system
4. long post-gang adrenergic fibers innervate cells of myenteric and submucosal plexuses
5. Afferent fibers in gut will send signals back to spinal cord via prevertebral gang.
6. About 50% of fibers present in sympathetic nerves to gut are affarent
***What are characteristics and functions of enteric Nervous System?
1. has as many neurons as spinal cord
2. located close to effector systems such as: SM, glands, and BVs (from esophagus to anus)
3. composed of two plexuses: A. myenteric plexus (Auerbach's) = motor functions: which increases intensity of contraction, tone, rate of contraction, and velocity of contraction B. Submucous plexus (Meissner's) = sensory functions which controls secretory activity, controls BF, and receives sensory input from chemoreceptors (osmolality, pH, etc) and mechanoreceptors (stretch)
What are chemical messengers for?
to communicate over a significant distance, and to communicate with organs that drain into the GI tract (Ex: gallbladder and pancreas)
*What are some classes of chemical messengers?
peptides: histamine and NO, small molecule neurotransmitters, and lipid mediators: prostaglandins and steroids
*Peptides are synthesized by _____ and packaged in _____?
enteroendocrine cells, nerve endings
*messengers designed to act over long distances are __________.
*Mediators that act over shorter distances are _____________ and _______________.
rapidly degraded; actively taken back into nerves for repackaging
***What are modes of communication?
1. Endocrine: long distance and cells produce messengers
2. Neurocrine: effects itself
3. Paracrine: short distances and binds to neighboring cells
4. Immune cells: juxtacrine regulation (mast cells = tissue equivelance as basophils in blood)
*What are hydrophobic molecules?
steroids and NO can traverse cell membranes and interact with intracellular targets (nuclear receptors)
*What are hydrophilic messengers?
peptides, neurotransmitters, PGs use classical receptor/second messenger pathways
*What do a majority of hydrophilic messengers bind to?
recepotrs linked to G-proteins with consequent increases in intracellular calcium or cyclic AMP (cAMP) [second messengers]
*What does the chemicial mediator, somatostatin, do?
acts at receptors, linked to inhibitory G proteins, that can antagonize increases in cAMP produced by other mediators (balances out actions of other peptides)
*Are chemical messengers hydrophobic or hydrophilic?
***The intestines are extremely well supplied with what?
cell types responsible for synthesis and release of hormones
***Hormones are __________________ within the wall of the intestines
packaged within the secretory granules
***released in response to nervous activity as well as chemical and mechanical signals _______________
coincident with food ingestion
***Some endocrine cells have processes that sense the luminal contents and are activated to release their hormones in response to what?
acidity, osmolarity, or nutrients such as amino acids and free fatty acids
Are all of the currently known GI hormones peptides? What is important to remember about peptides?
yes. Not all peptides isolated from the GI tract are hormones
What are "candidate hormones"?
other GI peptides that have not yet fulfilled all of the criteria, yet which are suspected to have physiologic functions following thier release
What is the criteria that defines a GI hormone?
1. physiologic event in one segment of the GI system alters the activity of another
2. Effect persists after neural connections have been saved
3. A substance isolated from the site of stimualtion must reproduce the effect of the physiologic stimulus following injection into the bloodstream
4. hormone must be identified chemically and its structure confirmed by synthesis
***What are the five peptides that fill the criteria to be considered a hormone?
5. Glucose-dependent insulinotropic peptide (GIP)
***Where is Gastrin produced?
***Where is CCK and secretin found?
duodenum, jejunum, and ileum
***Where is GIP and motilin found?
duodenum and jejunum
***What secretes, what is the stimulus, and what actions does gastrin do?
1. G cells
2. stomach distention and acid pH
3. increases HCl production in stomach, gastric motility, stimulates growth of gastric mucosa, contract lower esophageal sphincter, and relaxes pyloric sphincter
****What secretes, what is the stimulus, and what actions does secretin do?
1. S cells
2. Acid chyme in SI
3. stimulate secretion of pancreatic juice and bile that is rich in bicarbonate ions- neutralise acid from stomach, inhibit production of HCl in stomach, promote growth and maintenance of pancreas, enhance effects of CCK, and increases rate of bile secretion by hepatocytes (cells in liver)
**What is chyme?
suspension of semi-digested food
***What secretes, what is the stimulus, and what actions does CCK do?
1. CCK cells
2. chyme rich in AAs, triglycerides, and fatty acids enter the SI
3. increases secretion of pancreatic juice rich in digestive enzymes, opens the sphincter of Oddi, contracts the gallbladder, and inhibits gastric secretion and motility
***What secretes, what is the stimulus, and what actions does GIP do?
1. enteroendocrine cells
2. chyme rich in triglycerides, fatty acids, and glucose enter the SI
3. stimulates release of insulin by beta cells, inhibits gastric secretion and motility, stimulates lipogenesis by adipose tissue, and stimulates glucose use by skeletal muscle cells
***What secretes, what is the stimulus, and what actions does motilin do?
1. mo cells
3. participates in controlling pattern of SM contractions in SI, and increases GI motility and stimulates the production of pepsin
1. act only in immediate area of their relaese
2. additional layer of control, particularly in response to changes in local condtions
3. Paracrine regulators, like neurotransmitters, are short acting
4. A special case of paracrine regulation is called autocrine communication- release of a substance, which then acts back on its cell of origin
***What secretes, what is the stimulus, and what actions does somatostatin do?
1. D cells
2. continuously released, in response to H+ ions in lumen
3. inhibits release of gastrin and reduces gastric acid production. Inhibition of vagal stimulation
What is the purpose of somatostatin?
exert opposite effect to metiators to balance out all others.
***What secretes, what is the stimulus, and what actions does histamine do?
1. mast cells (= to basophils)
2. continuously released, in response to H+ ions in lumen
3. inhibits release of gastrin and reduces gastric acid production and inhibition of vagal stimulation
(hand in hand with somatostatin)
1. Chemical messengers are synthesized in neurons of GI tract
2. Stored in nerve endings and released on receipt of an eletrical signal
3. Diffuse across synaptic clefts to exert their effects on effector cells of GI
4. Neurotransmitters are short acting and cover short distances
***What secretes, what is the stimulus, and what actions does VIP do?
1. produced by neurons in mucosa
2. chyme entering the SI
3. stimulates buffer secretion (suppresses bicarbonate), inhibits gastric acid secretion, and relaxation of GI SM
***What secretes and what actions does bombesin (GRP = gastrin releasing peptide) do?
1. produced by vagus nerve that innervate the G cells
2. stimulates gastrin release from G cells, bridge the gut and brain (through neurocrine means) to inhibit further food intake
***What secretes and what actions does enkephalins do?
1. produced by nerves in GI mucosa
2. stimulates contraction of SM- @ sphincters, inhibits intersinal secretion of fluid and electrolytes (basis of use of opiates in rxn of diarrhea (loss of H2O and electrolites)
1. Mediated by release of substanes by cells of mucosal immune system
2. activated by antigenic products of microorganisms
3. release a variety of chemical mediators including amines (histamine), prostaglandins, and cytokines
4. important in sensing a threat (invasion of mucosa by pathogens)
5. may also be responsible for intestinal dysfunction in setting of inflammation or conditions such as food allergies
What is Zollinger-Ellison Syndrome (gastrinoma)?
1. non-beta cell tumors of pancreas or duodenum- increase gastrin production so lot of hydrochloric acid fromed
2. decreases ability of liver and pancreas to neutralize acid in gut- ulcerations (duodenal ulcers)
3. decrease ability to absorb digested products due to damage to gut wall and inactivation of pancreatic digestive enzymes, especially pancreatic lipase, so there is an increased presence of fat in stools = steratorrhea
4. have precipitation of bile salts = osmotic diarrhea
5. treatment is gastrectomy (removal of stomach) or proton pump inhibitors (amined at K+/H+ ATPase)