[08.24] Hormonal Regulation of Digestion V2

Autocrine

Which hormone classification involves a mediator binding to the cell that produced it?

Paracrine

Which hormone classification involves a mediator binding to neighboring/adjacent cells?

Endocrine

Which hormone classification involves a mediator traveling through the bloodstream to affect distant organs?

Neurocrine

Which hormone classification involves hormone secretion mediated by nerve signals?

G-cells in the stomach antrum and duodenum

What cells primarily secrete gastrin?

Breakdown products of protein digestion, distention of stomach, vagal nerve stimulation

What are the three main stimuli for gastrin secretion?

Increases HCl secretion

What is a primary function of gastrin?

Positive feedback loop

What type of feedback loop occurs with gastrin secretion?

Acetylcholine, histamine, and gastrin

What are the three stimulations for parietal cells to release HCl?

Proton pump inhibitors

What type of drug inhibits the production of more acid?

H2 receptor blocker

How do Cimetidine, Ranitidine, and Famotidine work in the stomach?

Stimulates H+ secretion by parietal cells, trophic growth effects, gastrocolic/gastrocecal reflex

What are the actions of gastrin?

Secretin and GIP

What hormones have an inhibitory effect on gastrin?

H+

What inhibits gastrin?

False

True or False: Gastrin secretion is stimulated by stomach distention and digestion of lipids

True

True or False: Increased H+ acts as a negative feedback on gastrin secretion.

Chyme containing amino acids and fatty acids

What is the main stimulus for CCK secretion?

Intestinal epithelial cells (enteroendocrine I cells), intestinal wall/epithelium, and brain

Where is CCK primarily synthesized?

C-terminus

Where does the biologic activity of CCK reside?

CCK-4, CCK-8, CCK-12, CCK-22, and CCK-58

What are the different forms of CCK?

CCK-8

Which form of CCK is sulfated?

CCKA and CCKB

What are the two main types of CCK receptors?

Sulfated CCK

What is the preferred ligand of the CCKA receptor?

Gastrin ≈ CCK

What is the preferred ligand of the CCKB receptor?

Stimulation of bicarbonate secretion, gallbladder emptying, inhibiting gut motility

What are the main functions of the CCKA receptor?

Regulation of nociception, anxiety, memory, and hunger

What are the main functions of the CCKB receptor?

Secretion of pancreatic juice and bicarbonate, contraction of gallbladder, relaxation of sphincter of Oddi, slows gastric emptying

What are the actions of CCK?

Hypothalamus

Where does CCK produce satiety?

False

True or False: CCK-4 is the sulfated form of CCK.

I cells

What type of cells secrete CCK?

False

True or False: CCK relaxes the gallbladder wall.

S cells in the duodenum

What cells secrete secretin?

H+ from chyme and fatty acids

What are the stimuli for secretin secretion?

27 AAs

How many amino acids are in secretin?

Inhibits gastrin and H+ secretion, and growth of stomach mucosa

What does secretin inhibit?

Neutralizing acidity of chyme in duodenum, trophic effect on pancreas, enhances effects of CCK

What are the main actions of secretin?

Neutralizing acid from the stomach and stopping its production

What is the main function of secretin?

False

True or False: Secretin has a trophic effect on the endocrine pancreas.

K cells of the duodenum and jejunum

What cells secrete GIP?

Glucose, amino acids, and fatty acids

What are the stimuli for GIP secretion?

Stimulation of insulin secretion

What is the main function of GIP?

Decreases gastric acid secretion and slows gastric emptying

What are the minor functions of GIP?

Adipose and muscle cells

What cells have GLUT4, which is an insulin-regulated glucose transporter?

L cells

What cells produce and secrete GLP-1?

Presence of hexose and fat

What stimulates GLP-1 secretion?

Decreases gastric emptying, induces satiety, increases sensitivity of ß cells to glucose

What are the actions of GLP-1?

Mo cells in the proximal small intestine

What cells secrete motilin?

Fasted state

When is motilin cyclically released?

Increases GI motility, stimulates the migrating motility complex

What are the actions of motilin?

Ingestion of food

What inhibits motilin?

Every 90 minutes

How often does motilin move through the fasting stomach and small intestine?

True

True or False: In a fasted state, Motilin is secreted by Mo cells

Autocrine, paracrine, endocrine, and neurocrine

What are the four major classifications of hormones?

Stomach antrum and duodenum

Where is gastrin secreted?

Increase HCl secretion in parietal cells

What is the main action of gastrin?

I cells in the small intestine

What cells secrete CCK?

Release of pancreatic enzymes and bile into the duodenum

What does CCK stimulation lead to?

CCK-8 and CCK-4

What are the two main active forms of CCK?

Neutralizes the acidity of chyme in the duodenum

What is the main action of secretin?

K cells in the duodenum and jejunum

What cells secrete GIP?

Stimulate secretion of insulin

What is the main action of GIP?

L cells

What cells produce and secrete GLP-1?

Induces satiety and decreases gastric emptying

What are the main actions of GLP-1?

Mo cells in the proximal small intestine

What cells secrete motilin?

Increases gastric motility

What is the main action of motilin?

To provide more time for enzymes to break down food in the small intestine

Why does the CCKA receptor slow down motility?

False

True or False: Gastrin stimulates trophic growth on the foregut and midgut organs

True

True or False: Gastrocolic reflex is stimulated by gastrin

False

True or False: Secretin serves to neutralize acid in the stomach, as well as stop its production

False

True or False: GIP is important especially for adipose and muscle cells since they have GLUT4. This is because GIP inhibits insulin secretion

False

True or False: CCK slows gastric emptying by promoting relaxation of the pyloric sphincter.

True

True or False: In endocrine hormones, the mediator travels through the bloodstream first before reaching the target organ. For neurocrine hormones, the products usually come from a nerve

The HCl in chyme and when chyme pH < 4.5

What stimulates secretin?

It is stimulated by consuming food

What is not a characteristic of Motilin

Trophic growth effects on mucosa of SI, colon, and liver

What is not an action of gastrin

The cell that makes the hormone is also a target cell of that hormone

What is characteristic of Autocrine hormone?

A cell makes the hormone and the target cell/s is/are the adjacent cell/s

What is characteristic of Paracrine hormone?

The target cells in endocrine are much farther away

What is characteristic of Endocrine hormone?

Products come from a nerve (usually at the axon terminal)

What is characteristic of Neurocrine hormone?

Main endocrine regulator of the secretory response to meals

What is the role of gastrin?

Most potent stimulants are Tryptophan and phenylalanine

What breakdown products of protein digestion are most potent for gastrin secretion?

Vagal nerve stimulation via gastrin-releasing peptides (GRP)

What type of interaction is this for gastrin secretion?

Stimulates histamine synthesis and release from oxyntic mucosal enterochromaffin-like cells (ECLs)

How does gastrin stimulate HCl secretion by parietal cells?

CCK-B or gastrin receptor

What other names does CCK2 receptor have?

Main function of this pathway is to increase acidity within the stomach

What is the main function of the gastrin secretion pathway?

Increase acidity within the stomach, helps kill foreign bacteria, activates pepsinogen

What does the positive feedback loop of gastrin achieve?

Carbonic anhydrase

What enzyme acts on Carbonic acid (H2CO3) to become bicarbonate and H+?

Bicarbonate goes into the blood circulation, which acts as a buffer to maintain optimum pH of blood

Why is Bicarbonate important in the HCl secretion pathway of parietal cells?

(+) Stimulates H+ secretion by parietal cells, (+) Trophic growth effects on mucosa of SI, colon, and stomach, (+) Gastrocolic/Gastrocecal reflex

What are the positive actions of gastrin?

When the stomach gets stretched, gastrin is released and travels to the bloodstream then to the cecum, causing the cecum to contract/move to create more space

What is the Gastrocolic/Gastrocecal reflex?

Cimetidine, Ranitidine, and Famotidine

Which drugs are H2 receptor blockers?

Acts as a H2 receptor blocker, stopping histamine from activating the parietal cell

How does cimetidine stop hyperacidity?

Inhibiting the production of more acid

How do proton pump inhibitors stop hyperacidity?

Does not work against the acid already in the stomach

What is the limitation of proton pump inhibitors?

Stimuli for secretion: chyme containing amino acids and fatty acids; Main stimulus for delivery of pancreatic enzymes and bile into the duodenum

What are the main functions of CCK stimulus?

Most abundant neuropeptide in the CNS

What is a characteristic of CCK in the brain?

Preprocholecystokinin is a 150 AA precursor; CCK has several forms depending on the number of AA residues after post-translational modification

What are the characteristics of CCK synthesis?

Pentagastrin: 5 AA chain

What is a characteristic of the biologic activity of CCK at the C-terminus?

CCK-8 is the sulfated form of CCK which has a sulfate tyrosine residue attached in the 7th position; CCK-4 exerts the same effects as the sulfated form

What are the main characteristics of the active forms of CCK?

Is important in attaching to the main CCKA receptor

What is the role of the sulfate tyrosine residue in CCK-8?