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Titolo:
Pepsinogens: Physiology, pharmacology pathophysiology and exercise
Autore:
Gritti, I; Banfi, G; Roi, GS;
Indirizzi:
Univ Milan, Ist Fisiol Umana 2, Dipartimento Sci Preclin LITA Vialba, Fac Med & Chirurg, I-20157 Milan, Italy Univ Milan Milan Italy I-20157 , Fac Med & Chirurg, I-20157 Milan, Italy Serv Med Sport & Lab, Castellanza, Varese, Italy Serv Med Sport & Lab Castellanza Varese Italy Castellanza, Varese, Italy
Titolo Testata:
PHARMACOLOGICAL RESEARCH
fascicolo: 3, volume: 41, anno: 2000,
pagine: 265 - 281
SICI:
1043-6618(200003)41:3<265:PPPPAE>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
GASTRIC CHIEF CELLS; SERUM GASTRIN; GUINEA-PIG; GASTROINTESTINAL SYMPTOMS; ACID-SECRETION; INOSITOL TRISPHOSPHATE; ANESTHETIZED RATS; FREE TESTOSTERONE; INTRAGASTRIC PH; PEPTIC-ULCER;
Keywords:
pepsinogen A; pepsinogen C; aspartic proteinases; gastric diseases; marathon; high altitude;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
123
Recensione:
Indirizzi per estratti:
Indirizzo: Gritti, I Univ Milan, Ist Fisiol Umana 2, Dipartimento Sci Preclin LITA Vialba, Fac Med & Chirurg, Via GB Grassi 74, I-20157 Milan, Italy Univ Milan Via GB Grassi 74 Milan Italy I-20157 57 Milan, Italy
Citazione:
I. Gritti et al., "Pepsinogens: Physiology, pharmacology pathophysiology and exercise", PHARMAC RES, 41(3), 2000, pp. 265-281

Abstract

Human gastric mucose contains aspartic proteinases that can be separated electrophoretically on the basis of their physical properties into; two major groups: Pepsinogen I (PGA, PGI); and Pepsinogen II (PGC, PGII). Pepsinogens consist of a single polypeptide chain with molecular weight of approximately 42 000 Da. Pepsinogens are mainly synthesized and secreted by the gastric chief cells of the human, stomach before being converted into the proteolytic enzyme pepsin, which is crucial for the digestive processes in the stomach. Pepsinogen synthesis and secretion are regulated by positive and negative feed-back mechanisms. In the resting state pepsinogens are stored ingranules, which inhibit further synthesis. After appropriate physiologicalor external chemical stimuli, pepsinogens are secreted in the stomach lumen where hydrochloric acid, secreted by the parietal cells, converts them into the corresponding active enzyme pepsins. The stimulus-secreting couplingmechanisms of pepsinogens appear to include at least two major pathways: one involving cAMP as a mediator, the other involving modification of intracellular Ca2+ concentration. Physiological or external chemical stimuli acting through the intracellular metabolic adenyl cyclase are more effective ininducing 'de novo' pepsinogen synthesis than those acting through intracellular Ca2+. The activation of protein kinase C (PK-C) would appear to be involved in regulatory processes. The measurement of pepsinogens A and C in the serum is considered to be one of the non-invasive biochemical markers for monitoring peptic secretion and obtaining information on the gastric mucosa status of healthy subjects. Recently, pepsinogen measurements have been used as an effective biochemical method for evaluating and monitoring patients with gastrointestinal diseases and for checking the effects of drug treatment. The level of PGA in the serum is always high in normal gastritis, while in atrophic gastritis it is always low. In both cases the PGC level inthe serum is high. In most gastrointestinal pathologies the ratio between the PGA/PGC decreases. Various reports concerning hormone and/or enzyme modification as well as gastrointestinal distress in the case of long distanceexercise have been reported. It has been suggested that the origin of the gastrointestinal distress experienced by long distance runners is a transient ischaemia of the gastric mucosa; it is also suggested that a hypobaric-hypoxic environment could contribute to induce gastric mucosa necrosis. Interrelation between gastrointestinal distress, hypobaric-hypoxic environment and modifications of PGA and PGC, gastrin and cortisol was evaluated in 13 athletes after a marathon performed at 4300 m. Gastrointestinal symptoms occurred in approximately 40% of the athletes. After the race the athletes showed a significant increase of gastrin and cortisol, while the ratio between PGA/PGC decreased. No relationship was observed between gastrointestinal symptoms and hormonal changes after the race. A control group of five subjects, who had been exposed to the same environmental conditions, showed no gastrointestinal or hormonal alteration. Conversely, control subjects presented a significant decrease of cortisol related to the circadian rhythm. Thesame incidence of gastrointestinal symptoms at high altitude and at sea level and the absence of pathological alteration of PGA and PGC in the serum of the athletes indicates that running a marathon and living for 6 days at 4300 m does not induce gastric mucosa necrosis. Cortisol and gastrin alteration observed in the athletes at this altitude would seem to be related to an activation of the mesopontine and forebrain structures involved in the behavioural and metabolic integration of the autonomic control and arousal and psychophysical-exercise stress. (C) 2000 Academic Press.

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Documento generato il 02/04/20 alle ore 09:06:33