Regulators of GI Function (Part II)

Question 1

What cells secrete Gastrin and where are they found? Name 3 effects that this EEC hormone has.

Answer 1

G-cells found in the stomach secrete Gastrin. This hormone acts DIRECTLY on parietal cells via CCK-2 receptors to secrete gastric acid. It INDIRECTLY acts on enterochromaffin-like (ECL) cells to release histamine that also acts on parietal cells. It also stimulates gastric motility and mucosal proliferation (ECL and parietal cells).

Question 2

What is the significance of histamine when it comes to gastric acid?

Answer 2

Histamine released from ECL’s provide a HUGE boost for acid production when it stimulates parietal cells.

Question 3

List 3 factors that can directly or indirectly increase acid production in the stomach.

Answer 3

1. Gastrin - targets ECL cells to produce histamine (indirect) or directly stimulates parietal cells
2. Gastrin-releasing peptide (Bombesin) - direct path
3. Acetylcholine - vagal activation stimulates MULTIPLE responses to regulate acid secretion.

Question 4

Protein-rich meals, high gastric pH, distension and G-RP can __________ gastrin release. On the other hand, fasting, a low gastric pH, somatostatin and CCK can ______ gastrin release.

Answer 4

Stimulate;

Inhibit

Question 5

What things or events might trigger the hypertrophy of glands and elongation of parietal cells in the stomach?

Answer 5

Long-standing proton-pump inhibitor (PPI) use, high levels of gastrin in circulation, frequent use of Zantac (histamine-2 blocker).

Question 6

Describe the mechanism by which PPIs can cause a an ECL tumor or gastrinoma.

Answer 6

Long-standing use of PPIs create a chonic low-acid leading to G-cell hyperplasia that produces more gastrin. High levels of gastrin might stimulate an ECL tumor which makes more histamine that acts on parietal cells to increase acid production. This has a trophic effect.

Question 7

What cells secrete Cholescystokinin (CCK) and where are they found? What are its effects?

Answer 7

I cells that are concentrated in the duodenum (and brain) secrete CCK. The predominant form, CCK-58, binds to CCK-1 receptor in the gallbladder and stomach. This stimulates gallbladder contraction, relaxes the Sphincter of Oddi and delays gastric emptying. It also stimulates the delivery of pancreatic enzymes from the acinus into the duodenum.

Question 8

What are the 2 major forms of Gastrin and their significance? Describe any unique features regarding it’s synthesis.

Answer 8

G-17 is the predominant form that can be measured after meals (post-prandial). G-34 has a longer half-life (30 minutes) and can be better measured when fasting. Active hormone gastrin is generated from the “prepropeptide” that is Preprogastrin. The terminal 4-amino acid sequence is bioactive.

Question 9

What factors are involved with the movement of bile from the gallbladder into the duodenum?

Answer 9

Nitric oxide and VIP from vagal afferents relax the Sphincter of Oddi. Whereas, ACh and CCK cause smooth muscle contraction within the gallbladder.

Question 10

List and summarize the 4 actions of CCK in the foregut.

Answer 10

1. promotes delivery of bile - contraction of gallbladder SM and relaxation of Sphincter of Oddi
2. promotes delivery of pancreatic enzymes from acinus into duodenum
3. inhibits gastric emptying - reduces rate of SMC contraction contributing to satiety (feeling full) after eating
4. inhibits acid secretion

Question 11

Describe how CCK secretion is regulated.

Answer 11

Intraluminal peptides in the small intestine stimulates CCK-RP and Monitor peptide from the pancreas (vagal stimulation) acts on I-cells to release CCK. This can be down-regulated by the pancreatic Trypsin enzyme that digests these peptides to shut off the CCK boost. This autoregulatory mechanism fine-tunes the amount of CCK released.

Question 12

What is the significance of S-cells and what do they secrete? What are the effects of its product? What is the regulatory feedback?

Answer 12

S-cells are pH sensors that activate with low pH in the duodenum. They release Secretin that increases HCO3- from pancreas and bile in order to bring up the pH. When the pH is at optimal level, this shuts off S-cells completing the feedback loop for pH control in small intestines.

Question 13

Where are S-cells found in abundance? What do they stimulate when activated? What effect does its hormone have on the stomach?

Answer 13

Duct cells, acinar cells of the pancreas, duodenum and bile ducs. These promote release of HCO3- when acid is present in the proximal small intestines. Secretin reduces acid secretion and delays gastric emptying.

Question 14

What is the molecular mode of action for Secretin on Cholangiocytes within the gallbladder?

Answer 14

Secretin increases cAMP that activates PKA. This process increases the conductance of the CFTR channel leading to a circular loop of Chloride that DRIVES HCO3- secretion into the lumen with the bile.

Question 15

What 2 factors stimulate Secretin secretion?

Answer 15

1. Acidification of the duodenal lumen that leads to pancreatic bicarbonate secretion.
2. Presence of Fatty acids

Question 16

What are D-cells and how does the presence of acid influence them?

Answer 16

D cells are the least abundant of all enteroendocrine cells. They secrete Somatostatin (isoforms S-28 and S-14) which has a major INHIBITORY effect on target cells. For example, it directly inhibits G-cells to reduce acid production.

Question 17

What effects does Somatostatin elicit in the foregut?

Answer 17

Somatostatin mainly decreases acid and pepsinogen secretion in the stomach by inhibiting G-cells when active. They also reduce secretions from the pancreas, gallbladder, and small intestine.

Question 18

What is the significance of Motilin? What makes it unique?

Answer 18

Motilin is released cyclically during a fasting state (interdigestive period). It mainly has a pro-kinetic effect on bowel motility. Motilin is involved with the rumbling of the stomach and migratory motor complex (phase 3 contractions) that cleans things outs in the GI tract (housekeeping function).

Question 19

What cells produce ghrelin and where are they found? What are the effects of ghrelin hormone?

Answer 19

A (X-like) cells secrete ghrelin which increases gastric contraction/emptying and appetite. High levels of ghrelin is associated with weight gain and growth hormone release. Levels rise when fasting and are effectively suppressed after high-carb meals.

Question 20

What is the new model as to why gastric bypass surgery is effective?

Answer 20

Gastric bypass allows ghrelin levels to fall which reduces the drive to eat more. This has effective appetite suppressant effects that enables sustainable weight loss after surgery.

Question 21

What are Serotonin (5-HT) Releasing Cells and where are they found?

Answer 21

Serotonin (5-HT)-releasing cells are highly distributed throughout the GI tract and produce serotinin. They are concentrated in the duodenum and rectum.

Question 22

What stimulates the release of serotonin from 5-HT cells? Describe the effects of serotonin in the GI.

Answer 22

Brushing mucosal cells along the villi of the small intestine initiates peristaltic and segmentation activity. Serotonin also plays a role in vasodilation of nearby blood vessels.

Question 23

The metabolism of what essential amino acid is associated with serotonin? What regulates its availability in the gut?

Answer 23

Metabolism of Tryptophan which is only obtained from diet regulates serotonin levels. The gut microbiome plays a major role in its availability and is thought to indirectly influence mood.