Abstract
Both receptor antagonists and acid pump inhibitors are clinically useful suppressants of acid secretion. The latter class of drugs, the substituted benzimidazoles, inhibit acid secretion more effectively and, therefore, provide superior symptom relief and healing in all acid-related diseases. The H2-receptor antagonists competitively block the action of histamine on the H2-receptors of parietal cells. This histamine is released from enterochromaffin-like cells (ECL cells) due to gastrin, acetylcholine or epinephrine stimulation. In addition, parietal cells have M3-receptors which can function independently of H2-receptors. Hence, there is no single common pathway for parietal cell stimulation. Stimulation of acid secretion by parietal cells requires activation of the acid pump, the gastric H+,K(+)-ATPase. The target site for the benzimidazoles is the activated gastric H+,K(+)-ATPase, and, in particular, the cysteines of the pump that are exposed to the acid space of the secretory canaliculus of the parietal cells. Pantoprazole in its protonated form selectively reacts with cysteines present in both the fifth and sixth membrane segments of the ATPase, explaining its mechanism of inhibiting proton transport by this enzyme.
Citations
Apr 29, 2006·Digestive Diseases and Sciences·Jai Moo Shin, George Sachs
Jun 1, 1994·Baillière's Clinical Gastroenterology·R E Pounder
Mar 5, 2004·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Laura CalabresiCesare Sirtori
Dec 16, 2000·Clinical Therapeutics·P W Jungnickel
Jun 3, 2011·Chemical Reviews·Eliezer J BarreiroCarlos A M Fraga
Aug 1, 1997·Alimentary Pharmacology & Therapeutics·M P WilliamsR E Pounder
Aug 10, 2000·Alimentary Pharmacology & Therapeutics·W P GeusC B Lamers
Nov 28, 2002·Alimentary Pharmacology & Therapeutics·T O G KovacsUNKNOWN Pantoprozole US Gerd Study Group B
Sep 30, 2000·British Journal of Clinical Pharmacology·R M MartinS Shakir
May 5, 2000·Fundamental & Clinical Pharmacology·C BlandizziM Del Tacca
Dec 13, 2005·Drugs·Juan V Esplugues
Jan 26, 2013·Journal of Neurogastroenterology and Motility·Jai Moo Shin, Nayoung Kim
May 16, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Joshua R LewisRichard L Prince
Jun 7, 1997·Lancet·D N Bateman
Aug 16, 2016·Pharmacology & Therapeutics·Nobuhiro InatomiKazuyoshi Otake
Jan 13, 2006·Biochemical Pharmacology·Jai Moo ShinGeorge Sachs
Mar 10, 2016·Molecular BioSystems·Chelsea J ParesiYue-Ming Li
Jul 11, 2006·British Journal of Clinical Pharmacology·Gianluca TrifiròUNKNOWN UVEC Group
Jul 22, 2018·European Journal of Gastroenterology & Hepatology·Md Mohaimenul IslamYu-Chuan Jack Li
Jan 11, 2013·Physiological Reviews·Sascha Kopic, John P Geibel
Apr 24, 2017·European Journal of Clinical Pharmacology·Hsien-Feng LinShih-Wei Lai
Nov 24, 1999·The American Journal of Physiology·C PrinzM Gratzl