Gastric mucosal protection: from prostaglandins to gene-therapy.
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.
Gyires
K
K
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, 1089. Budapest, Nagyvárad tér 4. Hungary. GYIRKLA@pharma.sote.hu
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D011453:Prostaglandins / Q000235:genetics / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000628:therapy*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism
D016228:Endothelial Growth Factors; D018836:Inflammation Mediators; D011453:Prostaglandins; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide