Induction of Secretagogue Independent Gastric Acid Secretion via a Novel Aspirin-Activated Pathway

Abstract

Aspirin has been widely recommended for acute and chronic conditions for over 2,000 years. Either single or repetitive doses are commonly used for analgesic and antipyretic reasons and to prevent heart attacks, stroke, and blood clot formation. Recent studies show that it can also be used chronically to dramatically reduce the risk of a variety of cancers. However, prolonged usage of aspirin can cause severe damage to the mucosal barrier, increasing the risk of ulcer formation and GI-bleeding events. In the present study, we show the effects of acute low-dose aspirin exposure as an active secretagogue-inducing gastric acid secretion. Studies were carried out with isolated gastric glands using the pH-sensitive dye BCECF-AM to assess acid secretion. The non-selective NOS inhibitor L-NAME (30 μM), or the specific inhibitor ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one) was applied while monitoring intracellular pH. The effects of basolateral exposure to aspirin (acetylsalicylic acid, ASA) caused activation of gastric acid secretion via the H+, K+-ATPase. Our data suggest that aspirin increases nitric oxide (NO) production, which in turn activates acid secretion. Exposure of gastric glands to either the non-selective NOS inhibitor L-NAME, and the highly selective, soluble guanylyl cyclase inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) effectively inhibited aspirin-dependent gastric acid secretion. Aspirin can be considered as a novel secretagogue, in the way that it activates the H+, K+-ATPase. With increased daily aspirin consumption, our findings have important implications for all individuals consuming aspirin even in low doses and the potential risks for increased acid secretion.

Efficacy and Safety of Novel Aspirin Formulations: A Randomized, Double-Blind, Placebo-Controlled Study

“…Furthermore, the dysregulation of nitric oxide (NO) production has been shown to contribute to the gastric lesions found in patients undergoing aspirin treatment. This fits with the evidence showing that aspirin induces inflammation in the gastric mucosa [28,29] as expressed by the dilatation of gastric microvessels.…”

Unveiling the potential effects of acetylsalicylic acid: insights into regeneration in endometrial stem cells

“…Intensive investigation of critical factors and cytokines that influence the quality of endometrial stem cells could lead to a better understanding of female infertility or repeated abortions that were previously unexplained. While there are various factors that can influence the functions of endometrial stem cells, the effects of acetylsalicylic acid have recently garnered attention due to its emerging regulatory functions in different disease conditions, such as cancers [28], gastric ulcers [29], hypertension [30], inflammation [31], and infertility [32]. Acetylsalicylic acid (also known as Aspirin) is one of the most potent and widely used medicines ever discovered [33].…”

Evaluating the role of muscular exercise in modulating the progress of peptic ulcer treated by quercetin or dexilant in male albino rats

“…In addition, another explaining mechanism is that dexilent is a modified PPI. These PPI medications irreversibly block hydrogen-potassium adenosine triphosphatase on the luminal side of the parietal cell, thus preventing secretion of hydrogen ions into the gastric lumen (Kitay et al, 2019).…”