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

GI: Regulatory Substances Flashcards by Monica Styrczula

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

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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**

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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 (+)

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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

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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

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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

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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

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Types of GI Regulatory Substances (3):

Hormones
Paracrines
Neurocrines

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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

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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

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“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
  *

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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 **

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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

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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

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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

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Gastrin (Functions)

(GI Hormone)

To acidify the lumen of the stomach in response to the ingestion of food
Stimulates acid secretion

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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

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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**

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Cholecystokinin (CCK) Functions:

GI Hormone

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Promotes pancreatic enzyme secretion
Promotes bile secretion
Inhibits gastric emptying
Generates satiety

Cholecystokinin (CCK) Targets:

GI Hormone

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Targets:

Gallbladder & Sphincter of Oddi
- Bile secretion
  - Contraction of the gallbladder
  - Relaxation of the Sphincter of Oddi
  - Trophic Effects (growth)
Pancreatic Acinar cells
- Production of enzymes required for digestion
  - Secretion of pancreatic enzymes
  - Secondary stimulation of HCO3-
  - Trophic effects exocrine pancreas
Stomach
- Inhibits gastric emptying
- Provides time for adequate digestion and absorption
Brain
- Role in regulating food intake
  - Satiety

Cholecystokinin (CCK) Regulation:

GI Hormone

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Stimulatory Events:

I-cells alerted to the presence of a meal with fat and protein that needs to be digested and absorbed
- CCK ensures that the necessary pancreatic enzymes and bile salts are secreted to aid in digestion and absorption
Fat is the most potent stimulator

Inhibitory Events:

Somatostatin release

Cholecystokinin (CCK) Actions:

GI Hormone

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Gall Bladder:

Bile Secretion
- Contraction of gall bladder & relaxation of the sphincter of oddi
- Ejection of bile into the lumen of the small intestine
  - Needed to emulsify and solubilize lipids
Trophic Effects:
- Growth of gall bladder

Pancreas:

Secretion of pancreatic enzymes
Secondary stimulation of HCO3- secretion
- Potentiates the effects of Secretin on HCO3-
Trophic effects
- Growth of exocrine pancreas

Brain:

Food intake regulation
- Satiety

Stomach:

Inhibition of gastric emptying
- Critical for fat digestion and absorption
Provides adequate time for digestion and absorption

Secretin

(GI Hormone):

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What is the critical regulator of digestion and absorption?

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Duodenal Cluster Unit

Biliary System
Pancreas
Duodenum

What is the major GI Peptide that functions as a paracrine regulatory substance?

* Somatostatin

**Inhibition of Gastrin Release:** **(GI Hormone)**

**Inhibitory Events:** * Acidification of the gastric lumen * Low pH of gastric contents * Somatostatin

**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

**Stimuli for CCK Release:** **GI Hormone**

* Digestion products of protein and fat * Fat is the most potent stimulator * Duodenum and Jejunum

**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

**Function of Secretin:** **GI Hormone**

* Neutralize the acid in the lumen of the small intestine

**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-

**Stimuli for Secretin Release:** **GI Hormone**

* Low intraluminal pH * Duodenal pH less than 4.5 * Fatty acids

**Inhibition of Secretin Release:**

* High pH * Somatostatin * Substance P

**What are the paracrines of the GI tract?**

* Somatostatin * Histamine Don't enter systemic circulation Made in the enteroendocrine cells

**Somatostatin Origin:** **(Inhibitory Paracrine)**

* Secreted by D-cells in the gastric and duodenal mucosa * Can be stored in the interneurons of the enteric nervous system

**Somatostatin Targets:** **Inhibitory Paracrine**

* Stomach * Intestine * Pancreas * Liver

**Regulation of Somatostatin:** **Inhibitory Paracrine**

Stimulated: * Decreased luminal pH Inhibited: * Vagal nerve stimulation

**Actions of Somatostatin:** **Inhibitory Paracrine**

Stomach: * Inhibits gastrin release * Inhibits histamine release * Inhibits acid secretion from parietal cells Intestine, Pancreas, Liver: * Inhibits release of CCK (GI Hormone)

**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

**Regulation of Histamine** **(Paracrine)**

* Stimulated by Gastrin * Inhibited by Somatostatin

**Histamine Actions** **(Paracrine)**

* Stimulates Acid Secretion

**Secretin Family of GI Hormones**

* GI Hormones * Secretin * Gastric Inhibitory Peptide * Neuropeptide * VIP * Bind to distinct receptors * G-protein coupled * Signal via increases in intracellular levels of cAMP

**The Motilin Family of GI Hormones:**

* Released in the fasting state * Responsible for stimulating GI motility in the interdigestive phase * Migrating Motor Complex * Clear the ingesta residues * Housekeeping post digestion and absorption

GI: Regulatory Substances Flashcards

(47 cards)