PHSL233
Lecture 05
Signal transduction in Epithelia II
This is signal transduction pathways
of a stomach parietal cells which is a
specilised epithelial cell. It secretes
acidic fluid to stomach to aid with
digestion.
Secretagons are ligands or
stimulatory agonist that will stimulate
this pathway to release acid,
histamine, acetylcholine and gastrin
are the main ones. All agonist are
working through GPCR, histamine is
working through adenylyl cyclase
whereas Ach and gastrin are working
through phosphatelipase C, but they
all leading to the same acidic
secretion effect.
The main inhibitory is somatostatin.
Histamine
Vagal nerve stimulates enteric nerve which stimulates enterochromaffin cells
(ECL) to release histamine. Closeby are parietal epithelial cells, histamine act on
H2 receptors (GPCR) on the basolateral membrane of the parietal epithelial cell.
This activates the alpha-s subunit and in turn adenylyl cyclase is excited causing
increase of cAMP and PKA levels.
PKA then phosphyorlates a H-K pump making a H-K -P pump. This will cause a
increase in acidic H+ to be pumped out of the cell while K is pumped in, thus
increase in transport rate. Due to the movement of H+, you will get Cl and water
following so ending up with HCl and water being secreted out of the cell into
lumen of stomach.
Acetylcholine
vagal nerve stimulates enteric nerves releasing
Ach, Ach can also directly stimulate the release
of histamine. Ach bind onto M3 receptor on
basolateral membrane (GPCR) of parietal
epithelial, note that GPCR always have 7
transmembrane domains. On binding of Ach on
the extracellular receptor, this will cause conformational change which change is transferred onto the G protein and thus
activating it. Alpha-q activates phosphatelipase C which produce DAG and IP3.
This then cause increase of Ca and in turn PKC which phosphorylates H-K pump
and causing excretion of HCL into lumenal stomach from parietal epithelial cell.
The pancreatic acinar cells secretes
enzymes which are essential for
digestion, there are also a lot of ligands
against stimulating signals with receptors
sitting in the basolateral membrane.
Resulting in secretion of HCO3
(bicarbonate) rich fluid on the apical
surface and into lumen of duct.
Ach, gastrin etc are all increasing
secretion whereas somatosatatin are
inhibiting secretion.
Secretin
main stimulis of secretin secretion is acid PH in the duodenum increased, acid fluid
is secreted in the stomach and enters the intestinal tract in which it must be
neutrilised by bicarbonate. So acinar cells of pancreas recognise this low PH, it will
secrete secretin which binds onto basolateral membrane of pancreatic duct
epithelial cells (M3 GPCR) and activating alpha-s. This in turn activating adenylyl
cyclase and increase cAMP and then PKA.
PKA then phosphorylates CFTR which is cystic fibrosis transmembrane
conductance regulator, mutation in this protein causes cystic fibrosis and it is a Cl
channel in pancreas but also transport bicarbonate (HCO3).
So CFTR-P is formed, this will start transport of bicarbonate and chloride out into
the lumen of duct, pancreatic duct epithelial cell secretes bicaronbate rich fluid into
lumen of du
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