Pepsinogens: Physiology, pharmacology pathophysiology and exercise

Human gastric mucose contains aspartic proteinases that can be separated el ectrophoretically on the basis of their physical properties into; two major groups: Pepsinogen I (PGA, PGI); and Pepsinogen II (PGC, PGII). Pepsinogen s consist of a single polypeptide chain with molecular weight of approximat ely 42 000 Da. Pepsinogens are mainly synthesized and secreted by the gastr ic chief cells of the human, stomach before being converted into the proteo lytic enzyme pepsin, which is crucial for the digestive processes in the st omach. Pepsinogen synthesis and secretion are regulated by positive and neg ative feed-back mechanisms. In the resting state pepsinogens are stored in granules, which inhibit further synthesis. After appropriate physiological or external chemical stimuli, pepsinogens are secreted in the stomach lumen where hydrochloric acid, secreted by the parietal cells, converts them int o the corresponding active enzyme pepsins. The stimulus-secreting coupling mechanisms of pepsinogens appear to include at least two major pathways: on e involving cAMP as a mediator, the other involving modification of intrace llular Ca2+ concentration. Physiological or external chemical stimuli actin g through the intracellular metabolic adenyl cyclase are more effective in inducing 'de novo' pepsinogen synthesis than those acting through intracell ular Ca2+. The activation of protein kinase C (PK-C) would appear to be inv olved in regulatory processes. The measurement of pepsinogens A and C in th e serum is considered to be one of the non-invasive biochemical markers for monitoring peptic secretion and obtaining information on the gastric mucos a status of healthy subjects. Recently, pepsinogen measurements have been u sed as an effective biochemical method for evaluating and monitoring patien ts with gastrointestinal diseases and for checking the effects of drug trea tment. The level of PGA in the serum is always high in normal gastritis, wh ile in atrophic gastritis it is always low. In both cases the PGC level in the serum is high. In most gastrointestinal pathologies the ratio between t he PGA/PGC decreases. Various reports concerning hormone and/or enzyme modi fication as well as gastrointestinal distress in the case of long distance exercise have been reported. It has been suggested that the origin of the g astrointestinal distress experienced by long distance runners is a transien t ischaemia of the gastric mucosa; it is also suggested that a hypobaric-hy poxic environment could contribute to induce gastric mucosa necrosis. Inter relation between gastrointestinal distress, hypobaric-hypoxic environment a nd modifications of PGA and PGC, gastrin and cortisol was evaluated in 13 a thletes after a marathon performed at 4300 m. Gastrointestinal symptoms occ urred in approximately 40% of the athletes. After the race the athletes sho wed a significant increase of gastrin and cortisol, while the ratio between PGA/PGC decreased. No relationship was observed between gastrointestinal s ymptoms and hormonal changes after the race. A control group of five subjec ts, who had been exposed to the same environmental conditions, showed no ga strointestinal or hormonal alteration. Conversely, control subjects present ed a significant decrease of cortisol related to the circadian rhythm. The same incidence of gastrointestinal symptoms at high altitude and at sea lev el and the absence of pathological alteration of PGA and PGC in the serum o f the athletes indicates that running a marathon and living for 6 days at 4 300 m does not induce gastric mucosa necrosis. Cortisol and gastrin alteration observed in the athletes at this altitude w ould seem to be related to an activation of the mesopontine and forebrain s tructures involved in the behavioural and metabolic integration of the auto nomic control and arousal and psychophysical-exercise stress. (C) 2000 Acad emic Press.