DIARRHEA OF FAMINE AND MALNUTRITION - INVESTIGATIONS USING A RAT MODEL .1. JEJUNAL HYPERSECRETION INDUCED BY STARVATION

The effects of progressive starvation for up to three days on the secretory functions of the intestine were investigated using in vitro and in vivo preparations of rat jejunum and secretagogues whose action was either through cyclic AMP or Ca++. Intitial starvation for 24 h (day 1) did not significantly alter the basal net electrogenic ion secretion measured in vitro as the short circuit current (Isc, μamps/cm2) or the change in electrogenic ion secretion (Δ Isc) induced by the secretagogues. By day 2 of starvation, however, the maximum Δ Isc transient induced by the cholinergic and other secretagogues (Δ Isc= Isc max-basal Isc) was greatly increased (up to a maximum of 117%) compared with the fed controls on an area basis. The Δ Isc were even greater on day 3 of starvation. It a tissue weight basis was used to normalise the data the increase became even more marked. The enhancement in secretion was not caused by a decrease in absorptive capacity as glucose, added mucosally, gave larger increases in absorptive currents in the starved than in the fed jejuna. Bethanecol dose-Δ Isc response curves in fed and starved jejuna showed an increase in the maximum electrogenic secretion in the starved but no apparent change in the affinity of their cholinergic receptors mediating the enhanced secretion. The starvation-induced increase in secretion elicited by bethanecol was blocked by atropine, indicating that the receptors were muscarinic, but was unaffected by tetrodotoxin indicating that the enteric neural innervation was not essential for its expression. Noradrenaline released by tyramine was greater in the starved than the fed jejunum, suggesting that a decreased sympathetic tone was unlikely to be the major cause of the starvation induced secretory enhancement. Measurement of jejunal fluid movements in vivo showed that in fed controls and throughout the three days of starvation there was an unchanged net fluid absorption in the basal, unstimulated state. By day 2 and day 3 of starvation, however, bethanecol stimulated fluid secretion was very much greater than that of the fed controls. This increase in fluid secretion was concomitant with significant increases in the concentration of chloride in the lumenal fluid. Starvation thus appears to make the rat jejunum hypersensitive to cholinergic and other secretagogues, increasing the electrogenic secretion of chloride in vitro and that of chloride and fluid in vivo. These results obtained with the rat model give a new insight into possible mechanisms by which the diarrhoea of human famine and malnutrition may be expressed.