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cAMP-dependent protein kinase catalytic subunit alpha cAMP-dependent protein kinase catalytic subunit beta cAMP-dependent protein kinase type I-alpha regulatory subunit cAMP-dependent protein kinase catalytic subunit gamma cAMP-dependent protein kinase type I-beta regulatory subunit cAMP-dependent protein kinase type II-beta regulatory subunit cAMP-dependent protein kinase type II-alpha regulatory subunit Prostaglandin E2 receptor EP3 subtype Adenylate cyclase type 10 Solute carrier family 12 member 6 Chloride anion exchanger Carbonic anhydrase 1 Liver carboxylesterase 1 Potassium- transporting ATPase subunit beta Potassium- transporting ATPase alpha chain 1 cAMP Misoprostol Acid H+ H+ K+ K+ Cl- Cl- Cl- Cl- HCO3- HCO3- Misoprostol Misoprostol Misoprostol Misoprostol Acid Misoprostol Acid Carbonic acid H+ CO2 H2O ATP PPi H2O Magnesium Gi signaling cascade Zinc (II) ion Cytosol Parietal Cell Lumen Misoprostol activates prostaglandin EP3 receptor which activates the Gi protein signaling cascade. Adenylate cyclase is inhibited therefore, cAMP production is reduced. cAMP activates protein kinase A, which activates the proton pump. Low cAMP concentration, results in less activated protein kinase A, therefore activation of the proton pump is reduced and less acid (H+) is pumped into the stomach lumen, reducing acidity. Blood Vessel Hepatocyte Cytosol Liver Stomach
PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PTGER3 ADCY10 SLC12A6 SLC26A3 CA1 CES1 ATP4B ATP4A cAMP Misoprostol Acid Hydrogen Ion Hydrogen Ion Potassium Potassium Chloride ion Chloride ion Chloride ion Chloride ion Hydrogen carbonate Hydrogen carbonate Misoprostol Misoprostol Misoprostol Misoprostol Acid Misoprostol Acid Carbonic acid Hydrogen Ion Carbon dioxide Water Adenosine triphosphate Pyrophosphate Water Gi signaling cascade
PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PTGER3 ADCY10 SLC12A6 SLC26A3 CA1 CES1 ATP4B ATP4A cAMP Mis Aci H+ H+ K+ K+ Cl- Cl- Cl- Cl- HCO3- HCO3- Cytotec Cytotec Cytotec Mis Aci Mis Aci CarbncA H+ CO2 H2O ATP PPi H2O Mg2+ Gi si c Zinc Cytosol Parietal Cell Lumen Misoprostol activates prostaglandin EP3 receptor which activates the Gi protein signaling cascade. Adenylate cyclase is inhibited therefore, cAMP production is reduced. cAMP activates protein kinase A, which activates the proton pump. Low cAMP concentration, results in less activated protein kinase A, therefore activation of the proton pump is reduced and less acid (H+) is pumped into the stomach lumen, reducing acidity. Blood Vessel