Gastric Mucosal Protection: From Prostaglandins to Gene-Therapy

Abstract

The maintenance of gastric mucosal function and integrity highly depends on the status of microcirculation. Vasoactive agents--prostaglandins, nitric oxide and sensory neuropeptides (e.g. calcitonin gene-related peptide)--play a crucial role in mucosal defensive processes. Beside the local release of vasoactive mediators the central nervous system is also involved in regulation of gastric functions. Cerebral lesions, stimulation of different brain areas can result in gastric mucosal injury. Noxious challenge of gastric mucosa alters the sodium currents in gastric sensory neurons and induces cfos mRNA expression in nucleus tractus solitarii and area postrema. Vagal nerve has long been established to play a permissive role in the development of gastric lesions. However, several lines of evidences suggest its physiological relevance in the enhancement of gastric mucosal resistance. It was concluded that gastroprotection can be induced by low level of central vagal stimulation and the consequent release of prostaglandins, nitric oxide, and calcitonin gene-related peptide. Prostaglandins, nitric oxide and sensory neuropeptides play a role also in ulcer healing by stimulating the formation of growth factors, the epithelial proliferation and angiogenesis. Both systemic and local administration of growth factors accelerated the ulcer healing. Local, single injection of plasmid-DNA encoding vascular endothelial growth factor (VEGF) was shown to stimulate the ulcer healing in the rat. The transient, local expression of VEGF in ulcerated tissue might be a new therapeutic strategy in the treatment of gastric ulcer disease.

Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

“…The dorsal vagal complex is likely to have a prominent role in conveying the centrally initiated effect to the periphery. It was shown that both vagotomy and atropine decreased the gastroprotective effects of centrally injected thyrotropin releasing hormone (TRH), adrenomedullin, peptide YY, opioid peptides, clonidine (for reviews see Gyires, 2005;Tache 2012), nociceptin, nocistatin and cannabinoids (Shujaa et al, 2009;Zádori et al, 2008). Pharmacological and biochemical studies have shown that activation of vagal cholinergic pathways stimulates gastric prostaglandin and NO release and the "efferent function" of capsaicin sensitive primary afferent fibers containing CGRP (Kato et al, 1994;Saperas et al, 1995;Yoneda and Tache, 1993).…”

Anti-gastric Actions of Eugenol and Cinnamic Acid Isolated from Cinnamomi Ramulus

“…7) Physiological factors of these gastric diseases include acid-pepsin secretion, parietal cell activity, mucosal barrier, mucus secretion, blood ‰ow, cell regeneration, and the release of endogenous protective agents, especially prostaglandins and epidermal growth factors. 8) One of the greatest concerns is to ascertain whether H. pylori-induced gastritis may lead to gastric cancer. According to several epidemiologic studies concerning the association between gastric cancer and H. pylori, the antibodies for H. pylori was increased and higher in the patients with gastric cancer than in the control group.…”

Effects of Pfaffia glomerata (Spreng) pedersen aqueous extract on healing acetic acid-induced ulcers

“…All of these factors contribute to and amplify the damaging effect of acetic acid on the glandular cells. Besides, nitric oxide (NO) plays a role also in ulcer healing by stimulating the formation of growth factors, the epithelial proliferation and angiogenesis (Gyires, 2005). It was observed that AEP enhanced the NOx levels (Freitas et al, 2004) and then increased the blood flow and stimulated some events for the mucosal regeneration.…”