Control of Gastric Acid Secretion in Health and Disease

The relationship between long-term proton pump inhibitor therapy and skeletal frailty

“…They are commonly used in the treatment of gastric esophageal reflux disease (GERD) and peptic ulcer disease, and serves as an effective prophylactic agent in patients treated concurrently with a non-steroidal anti-inflammatory drug (NSAID). PPIs act through irreversibly inhibiting the activity of Na+/K+/H+ pumps located on parietal cells of the gastric lumen, thus preventing the secretion of hydrogen ions into the gastric lumen [1]. As such, PPIs are able to raise the pH level of the gastric lumen, and prevent associated complications seen with such an acidic environment.…”

Basics of gastric acid secretion

“…М 3 -холинорецептор сопряжен с Gq-белком, за счет 3.1) которого происходит дальнейшая сигнальная трансдук-ция в клетке [2,6,28]. Происходит активация фосфоли-пазы С, которая катализирует расщепление мембранно-го фосфолипида фосфатидилинозитол-4,5-дифосфата (PIP2) на инозитолтрифосфат (IP3) и диацилглицерол (DAG) [28,29]. Инозитолтрифосфат открывает кальцие-вые каналы в эндоплазматическом ретикулуме, что вызывает увеличение концентрации ионов Cа 2+ в пари-етальной клетке.…”

“…), достигает парие-тальных клеток посредством сис-темного кровотока [2,3,9,10,19]. Его прямое стимулирующее дей-ствие реализуется через холецисто-кининовые ССК-B-рецепторы (CCK-2 по номенклатуре IUPHAR 1 ) на базо-латеральной поверхности париеталь-ной клетки, а опосредованное стиму-лирующее действие -через взаимо-действие с тем же подтипом рецеп-торов на ECL-клетке [2,6,9,28,29]. Процессы внутриклеточной сигналь-ной трансдукции и участвующие вторичные мессенджеры при акти-вации ССК-B-рецеп тора эквивален-ты вышеописанным при активации М 3 -холино рецептора [11,14].…”

Proton Pump Inhibitors Therapy for Eosinophilic Esophagitis

“…PPIs are prodrugs which become activated within that acid environment to a reactive species, the thiophilic sulfenamide. Then, this reactive species binds covalently with sulfhydryl groups of cysteines in the H + ⁄K + ATPase (cysteine alkylation) irreversibly inactivating the pump molecules [14,15], resulting in a specific and long-lasting impairment of acid suppression, regardless of other stimulating factors. PPIs are the most effective acid inhibitors currently available and are the most widely prescribed class of gastrointestinal medications [15].…”

“…Then, this reactive species binds covalently with sulfhydryl groups of cysteines in the H + ⁄K + ATPase (cysteine alkylation) irreversibly inactivating the pump molecules [14,15], resulting in a specific and long-lasting impairment of acid suppression, regardless of other stimulating factors. PPIs are the most effective acid inhibitors currently available and are the most widely prescribed class of gastrointestinal medications [15]. Currently, PPIs are the treatment of choice for all acid-related disorders including peptic ulcer disease, gastroesophageal reflux disease (GERD), eradication of Helicobacter pylori, prevention of ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs) and ZollingerEllison syndrome.…”