Lecture 11 Flashcards
In the GI tract, ______ and ________ signals promote the secretion of _______ and ______ from epithelia and associated organs
hormones
nerve
fluids
enzymes
Parietal epithelia secrete what into the stomach?
acid
What does the pancreas secrete?
digestive enzymes (from acinar cells) and bicarbonate rich fluid (from duct cells)
What are 5 cells inside the stomach?
Mucus cells Parietal cells enterochromaffin-like cell G-cell D cell
What is the purpose of the mucus cell?
to protect the other cells from the acid
What is the purpose of the parietal cell?
it secretes acid into the stomach
What is the purpose of the enterochromaffin-like cell?
these stimulate Parietal cells
What are two different ligands that are important for HCl secretion?
- ACh
- histamine
What is the advantage of having two ligands that can release HCl from the parietal cell?
- to get more acid secretion
- if one is not working, the other can take over
There are 4 steps to the histamine signal transduction pathway. What is the first one?
histamine binds to the H2 receptor in parietal cells
What happens after histamine binds to the H2 receptor in parietal cells?
This receptor is a GPCR and it dissociates and activates adenylyl cyclase to catalyse the conversion of ATP to cAMP which activates PKA. PKA phosphorylates the H+/K+ pump, promoting its exocytosis to the apical membrane. H+ is pumped out of the cell, as well as Cl- through the CFTR which causes an increase in HCl
What stimulates the release of histamine? Where is it released from?
The vagal nerve sitting in the brainstem stimulates the enteric nerve which activates ECL cells and then histamine is released from the enterochromaffin-like cells
What stimulates the release of ACh and where is it released from?
The vagal nerve sitting in the brainstem stimulates the enteric nerve which releases ACh.
What does ACh do? Where does it bind? What does this cause?
ACh binds to the M3 receptor which is a GPCR, there is the conversion of GDP to GTP and the activation of PLC. PLC breaks down PIP2 to IP3 and DAG. DAG activates PKC and IP3 binds to its receptor in the ER which leads to Ca2+ being pumped out of the ER. The combined effect of these two things leads to the activation of the H+/K+ pump which is exocytosed to the apical membrane. This allows HCL to be secreted into the lumen of the stomach
What is one way to treat acid reflux?
- through proton pump inhibitors (tablets) which bind to the H+/K+ATPase and is used to treat acid reflux
What is one way that we can get gastric ulcers or gastric cancer?
Helicobactor pylori is a bacteria which inhibits acid secretion if there is too much of it. This damages the epithelia and can damage the integrity of the epithelia and so holes start appearing. The acid that is there cal enter these holes so it promotes gastric ulcer formation and gastric cancer
For successful stimulation of hydrochloric acid secretion from stomach parietal epithelial cells:
A. Histamine is released from enterochromaffin-like (ECL) cells.
B. Histamine stimulates conversion of phosphatidyl inositol bisphosphate (PIP2) to diacylglycerol (DAG) and inositol triphosphate (IP3).
C. Histamine activates a GPCR, while acetylcholine does not
D. Vesicular H+/K+ATPase is endocytosed from the apical membrane.
A. Histamine is released from enterochromaffin-like (ECL) cells.
What are two important cells in the pancreas for secretion, and what do they secrete?
- acinar cells which secrete digestive enzymes which normally sit in zymogen granules
- ductal cells which secrete bicarbonate-rich fluid
What is the stimulus to release digestive enzymes from acinar cells?
cholecystokinin
What is the stimulus to release bicarbonate-rish fluid from ductal cells?
secretin
What is the stimulus for CCK secretion? Where does this occur?
When food components such as amino acids or fatty acids are detected in the small intestine, CCK is released from I cells in the small intestine
Explain how CCK stimulates the exocytosis of digestive enzymes from the acinar cells
CCK binds to the CCK1 receptor on the basolateral membrane of the acinar cells. This receptor is a GPCR: GDP is converted to GTP and PLC converts PIP3 to DAG and IP3. DAG activates PKC and IP3 activates Ca2+ channels in the ER. Together these help exocytose the zymogen granules from the vesicles into the lumen of the acinar cells.
What is the stimulus for secretin secretion? Where does this occur?
When the stomach is digesting food, the pH decreases in the small intestine but the small intestine can’t deal with the low pH so it secretes secretin from its S cells.
Explain how secretin stimulates the exocytosis of bicarbonate from the ductal cells
Secretin binds to S1 which is a GPCR. This activates adenylyl cyclase which breaks down ATP to cAMP, activating PKA. PKA phosphorylates CFTR which is exocytosed to the apical membrane of pancreatic ductal cells. HCO32- can leave through the CFTR
What are the two purposes of HCO32-?
It neutralises the acid from the stomach so the pH increases in the intestines. It also acts as a carried for enzymes moving into the SI
What is the issue with cystic fibrosis in terms of the HCO32-?
In cystic fibrosis, bicarbonate-rich fluid is absent or reduced
Describe the effect of cystic fibrosis on the secretion from the pancreas
In cystic fibrosis, the CFTR is absent of dysfunctional. Pancreatic duct cell secretes no (or a reduced amount of bicarbonate-rich fluid) into the lumen of the duct. This means there is no alkalisation of stomach acid and so we can’t move enzymes into the small intestine
Where can a good summary of kidney transduction pathways be found?
slide 21-26 of lecture 11
