H+,K+-ATPase

H+,K+-ATPase, known as a proton pump in the parietal cell, Secretion of hydrogen ion depends on the gastric H+/K+-adenosine triphosphatase (H+/K+-ATPase), or proton pump, which consists of α- and β-subunits. By electron microscopic histochemistry, the H+/K+-ATPase is found in cytoplasmic tubulovesicles of resting parietal cells, while it is localized on the membrane of secretory canaliculi in activated cells.

SCH 28080
76081-98-6
847574-05-4
Linaprazan
847574-05-4
855998-67-3
Linaprazan mesylate
855998-67-3
881681-00-1
Vonoprazan
881681-00-1

Background


An Overview of H+/K+-ATPase

H+/K+-ATPase (also named proton pump in the parietal cell) is a P-type cation transporter that binds to the surface of the cell membrane. H+/K+-ATPase uses the energy produced by ATP hydrolysis to drive ion exchange (proton, chloride and potassium) on both sides of the cell membrane. Proton pumps are mainly found in the cells of the stomach wall and the kidneys, and their functions are different. The proton pump of the kidney is mainly responsible for acidifying urine and reabsorbing potassium. The main proton pump in the human body is present on the cell membrane of the parietal cells of the gastric parietal cells. H+/K+-ATPase exchanges H+ and K+ with the energy provided by ATP degradation, specifically pumps H+ into the gastric cavity, acidifies the stomach contents, and forms a high acid state in the stomach.

Inhibition of H+/K+-ATPase

H+/K+-ATPase inhibitors (proton Pump inhibitors, PPIs), include irreversible inhibitors and reversible K+-competitive acid pump antagonists (P-CABs/APAs). Irreversible inhibitors include Sub-pump drugs such as timoprazole (TMZ), Ou Meprazole (OMZ), lansoprazole (lansoprazole, LSZ), rabeprazole (RBZ). The proton pump inhibitor mainly acts on the stomach H+/K+-ATPase to achieve the purpose of inhibiting gastric acid. It is mainly used for the treatment of diseases caused by excessive gastric acid secretion, such as gastric ulcer, duodenal ulcer, functional dyspepsia and gastroesophageal reflux disease.

H+/K+-ATPase and Diseases

Acid related disorders (ARDs) refer to gastrointestinal diseases that are caused by excessive gastric acid secretion or sensitivity to gastric acid. It mainly includes peptic ulcer disease (PUD), gastroesophogeal reflux disease (GERD) and functional dyspepsia (FD). Gastric acid secretion is involved in the secretion of H+/K+-ATPase on the tubular membrane of parietal cells. The accumulation of gastric acid in local tissue causes the pH to decrease, affecting the function of many metabolic enzymes in the cell, causing energy production disorders, and the active transport process of the cell membrane is abnormal, resulting in degeneration and necrosis of cells. In addition, too much H+ can also stimulate mast cells and cause histamine secretion. Histamine further increases gastric acid secretion by paracrine action on parietal cells, and histamine can also stimulate local tissues, causing telangiectasia, increased permeability, and eventually mucosal congestion, edema, hemorrhage, erosion and even ulceration.

Reference:

Li H., Meng L., Liu F., Wei J. F., Wang Y.Q. (2003) H+/K+-ATPase inhibitors: a patent review. Expert Opin Ther Pat. 23: 99-111.