GI: Regulatory Substances Flashcards
Neurocrines
(GI Peptides)
- Substances that are synthesized in the cell bodies of neurons of the GI tract
- Released following an AP
- After release, diffuses across the synapse and acts on target cell
GI Neurocrines:
- Acetylcholine (ACh)
- Norepinephrine (NE)
- Vasoactive Intestinal Peptide (VIP)
- Gastrin-releasing peptide (GRP)
- Enkephalins (Opiates)
Effector cells need to have a specific receptor for this neurocrine
Vasoactive Intestinal Peptide (VIP)
(Neurocrine)
Regulatory substance type: Neurocrine
Source = Neurons of the ENS
Actions:
Excitatory and inhibitory - depends on effector
- Relaxation of smooth muscle (-)
- Increase intestinal secretion (epithelial cells) (+)
- Increase Pancreatic secretion (+)
** Potent Vasodilatior**
Acetylcholine (ACh)
(Neurocrine)
Source = Cholinergic neurons
- Use NT ACh to send messages
Actions:
- Contraction of smooth muscle in GI wall (+)
- Relaxation of sphincters (-)
- Increase salivary secretion (+)
- Increase gastric secretion (+)
- Increase pancreatic secretion (+)
Gastrin-Releasing Peptide (GRP)
(Neurocrine):
Source = Neurons of the gastric mucosa
- Released following an AP in the GI tract
- Diffuses across the synapse to act on G-cells to release Gastrin
Actions:
- Increase gastrin secretion (+)
Example of the Enteric Nervous System activating the Endocrine System
Norepinephrine (NE)
(Neurocrine)
Source = Adrenergic Neurons
- Release NE as a NT messenger
- Post-ganglionic sympathetic neurons
Actions:
- Relaxation of smooth muscle in the GI wall
- Contraction of sphincters
- Increased salivary secretion
Paracrines
(GI Peptides)
- Don’t enter systemic circulation
- Peptides that are made and secreted by endocrine cells of the GI tract
-
Local action
- Within the same tissue that secretes them
- Substances reach their target cells via diffusion over short distances through interstitial fluid
Benefits= Quick, local response to local changes
Hormones
(GI Peptides)
Long distance action
- Peptides secreted from endocrine cells of the GI tract
- Secretion into blood (portal circulation)
- Target = GI tract or other organs in the body
GI Peptides Classified as Hormones:
- Gastrin
- Cholecystokinin (CCK)
- Secretin
- Gastric Inhibitory Peptide (GIP)
Benefits:
- Broad function
- Simultaneous Actions @ Multiple Sites
Types of GI Regulatory Substances (3):
- Hormones
- Paracrines
- Neurocrines
Qualifications to be considered a GI Hormone
- Secreted in response to a physiologic stimulus
- Carried in the bloodstream to a distant site
- Production of a physiologic action at distant site
- Function must be independent of any neural activity
- Must be isolated from the site of stimulation, purified and chemically identified
- Ability to be synthesized
- Can reproduce the effect of the stimulus when injected into the bloodstream at physiological levels
Synthesis & Release of GI Hormones
Synthesis:
- Enteroendocrine cells (specialized)
- GI Endocrine Cells @ various parts of GI tract
Release:
- Neural activity, chemical and mechanical signals associated with food ingestion
Enteroendocrine cells (on Villi) have an open morphology
- Contact with the intestinal lumen
- “Sample and Taste”
- Narrow apex
- “Store n’ Release”
- Broad Base
- Signal stimulus –> Hormone release to lamina proprina on basolateral side –> Bloodstream Transport
“Open” GI Endocrine Cell
Open morphology of the endocrine cells that contact the intestinal lumen (where stuff is flowing)
- Apical process = narrow apex & microvilli
- “Sample & Taste”
- Broad base of GI Endocrine cell
- “Store & Release”
- Location of hormones
- Stored in secretory granules
- Sense stimulus –> release to lamina proprina on basolateral side –> bloodstream transport
*
Distribution of GI Hormones
(Along GI Tract)
- Largest amount of GI hormones in the duodenum and jejunum
- Duodenum = Digestion
- Jejunum = Absorption
- Small amounts of GI hormones present in the ileum
- Reserved capacity function
- No GI hormones in Colon
** Only Gastrin in the Stomach **
Actions of GI Hormones
- Modify secretion, motility and cell growth in target organs
- Majority signal to GI tract segments that are distal to their site of release
- Some have a feedback reflex
- Signal back to GI segements that are proximal to their site of release
- ex. CCK
- Crosstalk for some
- Binding to receptors of nerve afferents
- Amplification of action via recruitment of neurocrines
Gastrin/CCK Hormone Family
- Initial sysnthesis as long peptides
- Sequentially cleaved to generate active forms
- Stored for release in response to physiologic stimuli
- Have identical C-terminal amino acids
- Bind to closely releated CCK1 and CCK2
- G-protein coupled receptors
- Respond to increases in cytoplasmic Ca2+
CCK2 receptor:
- Can bind CCK and Gastrin due to idental C-terminal amino acids
CCK2 Receptor (GI):
CCK2 receptor:
- Can bind CCK and Gastrin due to idental C-terminal amino acids
Physiological Conditions:
- CCK2 preferably binds Gastrin
- Larger [Gastrin] in bloodstreamcirculation
- CCK1 preferably binds CCK
- Complexity of side chains
Gastrin (Functions)
(GI Hormone)
- To acidify the lumen of the stomach in response to the ingestion of food
- Stimulates acid secretion
Gastrin (Actions):
GI Hormone
Actions:
- Direct
- Binds to CCK2 receptor on parietal cells
- Increase acid secretion
- Indirect
- Bind to CCK2 receptor on ECL cells
- Stimulate release of histamine
- Also stimulates acid secretion by the parietal cells
Stimuli for Gastrin Release:
(GI Hormone)
Stimulatory Events:
- Cephalic phase stimulation (vagus)
- Chewing, smell, taste
- Anticipation of food
- Prior to entry in the stomach
- Breakdown products of proteins
- Small peptides & AA’s
- Distal GI tract
- Physical Distension of the Stomach by food
** Appears in the Antrum of the Stomach, Duodenum and Jejunum**
Cholecystokinin (CCK) Functions:
GI Hormone
- Promotes pancreatic enzyme secretion
- Promotes bile secretion
- Inhibits gastric emptying
- Generates satiety
Cholecystokinin (CCK) Targets:
GI Hormone
Targets:
- Gallbladder & Sphincter of Oddi
- Bile secretion
- Contraction of the gallbladder
- Relaxation of the Sphincter of Oddi
- Trophic Effects (growth)
- Bile secretion
- Pancreatic Acinar cells
- Production of enzymes required for digestion
- Secretion of pancreatic enzymes
- Secondary stimulation of HCO3-
- Trophic effects exocrine pancreas
- Production of enzymes required for digestion
- Stomach
- Inhibits gastric emptying
- Provides time for adequate digestion and absorption
- Brain
- Role in regulating food intake
- Satiety
- Role in regulating food intake
Gastrin (Origin):
GI Hormone
- Released from the G-cells of the antral mucosa
- G-17
Cholecystokinin (CCK) Origin
GI Hormone
Release:
- From I-Cells in the duodenal and jejunal mucosa
Inhibition of CCK:
GI Hormone
- Somatostatin
What GI Hormone is the major regulator of the duodenal cluster unit and why?
CCK
- Pancreas, duodenum and biliary system
- Principal humoral regulator of enzyme secretion from pancreatic acinar cells
- Contracts gallbladder
- Relaxes the sphincter of oddi
- Slows gastric motility to dumb down emptying
Origin of Secretin:
GI Hormone
- Released from the S-cells in the duodenal mucosa
Targets and Actions of Secretin:
GI Hormone
“Nature’s Antacid”
Liver:
- Stimulates the secretion of bile
- Rich in HCO3-
Pancreas:
- Stimulates the secretion of HCO3-
- Trophic effects
Stomach:
- Inhibits gastric release
- Directly inhibits acid secretion
Duodenal Epithelium:
- Stimulates secretion of HCO3-
Histamine Origin:
(Paracrine: Not a Peptide)
- Enterochromaffin-like cells (ECL)
- Mucosal Mast Cells
- Immune cells
- Can receive multiple inputs
- Neurocrine
- Endocrine
- Physical
- Chemical Receptor
Histamine Targets:
(Paracrine: Not a Peptide)
- Depends on if it was released by ECL cell or mast cell
- Parietal cells of the stomach
- Released by ECL cells
- Immune Mediator
- Secretion by mast cells
