Lecture 11 - Signal transduction in Epithelia 2 (Gastro) Flashcards
What do hormones and nerve signals promote in the GI tract?
In GI tract hormones and nerve signals promote secretion of fluids and enzymes from epithelia and associated organs
What does parietal epithelia secrete?
Parietal epithelia secrete acidic fluid into stomach.
What does the pancreas secrete?
Pancreas secretes digestive enzymes (acinar cells) and bicarbonate-rich fluid (duct cells).
What activates the signal transduction pathways in stomach parietal cells?
Histamine
ACh
Ca2+
EGF TGF-a
Prostaglandin
Somatostatin
Gastrin
What stimulates histamine release from ECL cells?
- Vagal nerve stimulates enteric nerve which stimulates ECL cells
2.Histamine released from ECL cell
What receptor in stomach parietal cells does histamine bind to?
H2 receptor (GPCR) on basolateral membrane
What is the histamine signal transduction pathway in stomach parietal cells?
- Histamine binds H2 receptor (GPCR)
- AC catalyses the conversion of ATP to cAMP, activating protein kinase A (PKA)
- PKA phosphorylates the H+/K+ pump prompting its exocytosis to the apical membrane
- H+ is pumped out of the cell, as well as Cl- through CFTR to cause an increase in HCl
What is the ACh signal transduction pathway in stomach parietal cells?
- ACh binds to the M3 receptor GPCR, activates PLC
- PLC breaks down PIP2 into IP3 and DAG
- DAG activates PKC
- IP3 binds to its receptor in the ER, Ca2+ pumped out of ER
- H+/K+ pump exocytosed to apical membrane
What receptor does ACh bind to in stomach parietal cells?
M3 receptor (GPCR) on basolateral membrane
What does PLC do?
Breakdown PIP2 into IP3 and DAG
What does DAG activate?
PKC
What is PLC?
Phospholipase C
What does Helicobacter pylori inhibit?
Helicobacter pylori inhibits acid secretion and 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.
B - ACh not histamine
C - both activate GPCR
D - Exocytosis
What do acinar cells in pancreas secrete?
Acini – acinar cells secrete digestive enzymes.
What is the major stimulus of pancreatic acinar cells via?
Major stimulus is via CCK – cholecystokinin
What do pancreatic duct cells secrete?
Ductal cells secrete bicarbonate-rich fluid
What do duct cells secrete in response to?
Secretin
Where is CCK released from?
CCK release from I cells in small intestine
What is CCK?
cholecystokinin
What is CCK released in response to?
Food components e.g. amino acids, fatty acids detected in small intestine
What does CCK stimulate?
CCK stimulates exocytosis of digestive enzymes
What does CCK bind to?
CCK binds to CCK1 receptor (GPCR) which activates PLC
What is the CCK pathway?
- CCK binds to CCK1 receptor (GPCR), activates PLC
- PLC breaks down PIP2 into DAG and IP3
- DAG activates PKC
- IP3 causes the release of Ca2+ from the endoplasmic reticulum
5.Exocytosis of zymogen granules
Where is secretin released from?
Intestinal S cells
What is secretin released in response to?
Acid pH in duodenum
What is the secretin secretion pathway?
- Secretin binds to S1 (GPCR), activates AC
- AC breaks down ATP to cAMP, activating PKA
- PKA phosphorylates CFTR
4.CFTR exocytosed to apical membrane of pancreatic ductal cells
What happens to pancreatic duct cells in CFTR?
CFTR is absent or dysfunctional. Pancreatic duct cell secretes no (or a reduced amount of) bicarbonate rich fluid into lumen of duct
What does absent or reduced bicarbonate fluid mean for people with CF?
In CF: reduced fluid in duct, therefore no alkalinisation of stomach acid; can’t move enzymes into small intestine.
