Pharmacology: Gastric Secretion Flashcards
What cells in the gastric pits secrete pepsinogen?
Chief cells
What cells in the gastric pits secrete HCl?
Parietal cells
What cells in the gastric pits secrete mucous and bicarbonate?
Mucous cells
What cells in the gastric pits secrete histamine?
Enterochromaffin-like cells
What cells in the gastric pits secrete gastrin?
G cells
What cells in the gastric pits secrete somatostatin?
D cells
What 5 steps are involved in HCl secretion?
- Carbonic Anhydrase combines CO2 and H2O to form H2CO3
- H2CO3 is broken down into HCO3- and H+
- The H+ ion is transported out of the cell by the H+/K+ ATPase (proton pump) and K+ is transported into the cell
- HCO3- is transported out of the cell into the blood plasma by the Chloride-Bicarbonate Exchanger and Cl- ion is transported into the cell
- Cl- ion is then transported out of the cell with a K+ ion by the Chloride-Potassium Symporter
There is now H+ and Cl- ions in the lumen and they combine to form HCl
How does histamine increase gastric acid secretion? (3 steps)
- When stimulated by acetylcholine, enterochromaffin-like cells secrete histamine.
- Histamine binds to H2 receptors on parietal cell which activates adenylyl cyclase
- Adenylyl cyclase causes increased cAMP which increases the number of proton pumps thus increasing gastric acid secretion.
What triggers histamine release from enterochromaffin-like cells?
Acetylcholine
What does Histamine bind to on parietal cells?
H2 receptors
What does histamine binding to receptors on parietal cells cause?
activation of adenylyl cyclase
What effect does adenylyl cyclase have on parietal cells?
Increases cAMP which increases the number of proton pumps
What effect does acetylcholine have on parietal cells?
Increases gastric acid secretion
How does acetylcholine cause increased gastric acid secretion from parietal cells? (3 steps)
- Acetylcholine is released by parasympathetic cholinergic neurons and binds to Muscarinic M3 ACh receptors on parietal cells.
- ACh binding causes PLC (phospholipase C) activation
- This causes increased intracellular
Ca++ evoking cell signalling pathways that increase the number of proton pumps
Thus increased gastric acid secretion.
What specific effect does acetylcholine have when it binds to parietal cells?
activates Phospholipase C
What happens in the cell when PLC is activated?
Increased intracellular Ca++
What does increased intracellular Ca++ cause?
It evokes cell signalling pathways that increase the number of proton pumps
What does Acetylcholine bind to on parietal cells?
Muscarinic M3 ACh receptors
Outline the effect of gastrin on parietal cells (3 steps)
Gastrin increases gastric acid secretion.
- Gastrin is released from G cells and binds to CCK2 receptors on parietal cells.
- Gastrin binding to CCK2 receptors causes PLC activation.
- PLC activation causes increased intracellular Ca++ increasing the no. of proton pumps thus increasing gastric acid secretion.
What receptor does gastrin bind to on parietal cells?
CCK2 receptor
What effect does Gastrin binding to its receptor on parietal cells have?
Activates PLC
Outline the effect of somatostatin on parietal cells.
- Somatostatin is released by D cells and binds to SST2R receptors on parietal cells.
- Somatostatin binding to SST2R receptors inhibits adenylyl cyclase thus decreasing cAMP and gastric acid release.
Outline the effect of somatostatin on enterochromaffin-like cells
Somatostatin released from D cells binds to SST2R receptors on enterochromaffin-like cells resulting in reduced histamine release thus reduced gastric acid secretion from parietal cells.
What receptor does somatostatin bind to on parietal and enterochromaffin-like cells?
SST2R
What specific antiacids (drug names, molecular name and substance) reduce the symptoms of excessive HCl secretion?
Gaviscon and Peptac - NaHCO3-CaCO3 - sodium alginate
How do antiacids work?
- NaHCO3 breaks down and HCO3- molecule combines with H+ ion from HCl to form H2CO3 which breaks down to form H2O and CO2.
- CaCO3 breaks down and CO3(2-) molecule combines with 2H+ ions from HCl to form H2CO3 which breaks down to form H2O and CO2.
What effect do NSAIDs have on gastric acid secretion and how do they cause this?
They increase gastric acid secretion.
This is because NSAIDs inhibit COX-1 which produces prostaglandins. Prostaglandins (PGE2) inhibit histamine release so no prostaglandins means increased histamine release thus increased gastric acid secretion.
What is misoprostol and what is it used for?
Misoprostol is an analogue of prostaglandin E1 and is used for prophylaxis of NSAID-induced peptic ulcers. It is also used to induce labour.
What are the side effects of misoprostol?
- abdominal pain
- diarrhoea
Name 3 proton-pump inhibitors. (PPIs)
- lansoprazole
- omeprazole
- pantoprazole.
Outline the mechanism of action of proton pumps.
Proton-pump inhibitors irreversibly inhibit H+/K+-ATPase pumps thus reducing HCl secretion.
What 4 conditions are proton-pumps indicated for?
- benign gastric acid ulceration
- NSAID-associated gastric acid ulceration
- gastro-oesphageal reflux disease
- Zollinger-Ellison syndrome
What is a side effect of proton-pump inhibitors?
Increased pH of stomach so increased risk of infection of GI tract. (reduced defences)
Name 4 histamine 2 receptor antagonists.
- ranitidine
- cimetidine
- famotidine
- nizatidine
Outline the mechanism of action of H2 receptor antagonists.
They block the H2 receptors for histamine thus reducing gastric acid secretion. Complete block of H2 receptors results in rapid effect.
What are H2 receptor antagonists indicated for?
benign and NSAID-associated gastric ulceration.
What bacteria often causes peptic ulcers?
H.pylori
What is the treatment of H.Pylori infection and peptic ulcer?
PPI (proton-pump inhibitor) and antibiotics (clarithromycin and amoxicillin or metronidazole)