Diarrhoea of famine and malnutrition: investigations using a rat model. 1. Jejunal hypersecretion induced by starvation.

Abstract

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". Initial 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, [tamps/cm2) or the change in electrogenic ion secretion (A Isc) induced by the secretagogues. By day 2 of starvation, however, the maximum A Isc transient induced by the cholinergic and other secretagogues (A Isc=Isc max-basal Isc) was greatly increased (up to a maximum of 117%) compared with the fed controls on an area basis. The A Isc were even greater on day 3 of starvation. If 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-A 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.

Effects of tetrodotoxin and ion replacements on the short-circuit current induced by Escherichiacoli heat stable enterotoxin across small intestine of the gerbil (Gerbillus cheesmani)

“…This is in agreement with other studies using different animals All values express as mean ± SEM % changes and statistical significance (unpaired t test) are given for test groups against control; a: p ≤ 0.001 (Young et al1988, Young & Levin 1990, Chohen et al 1992, Carey et al 1994). The present study showed that starvation increases the Isc generated by STa across the jejunum both using stripped and unstripped preparations but the percent increases using the unstripped sheets were double that of the stripped ones.…”

Effects of Dietary Deprivation on Smalland Large Intestinal Ion Transport in the Mouse

“…In contrast to the mouse, in rat jejunum and ileum, starvatian for 48h and nh increased the electrogenic secretion induced by bethanechol and 5-HT in vitro (25,26,48,49). There might be several reasons for the deereased response to bethaneehol and 5-HT in ease of starvation by mouse small intestine compared to the rat, apart from just saying "species difference".…”

“…In vivo studies: A modification of the gravimetric method of Strombeck (45) by Young and Levin (48,49) was used to assess intestinal t1uid transport in vivo.…”

AÇ YE TOK FA~LE~E, MEDİAL JEJUNU~, . PROKSIMAL VE DISTAL ILEUMDA ASETILKOLININ OLUŞTURDUQU ~SI~MALAR İLEwE~DEE;DİLEN NON-KUMULATIF CEVAP EGRILERI

“…Bununla birlikte, insan ve rat ince bağırsağında in vi/ro yapılan çalışmalar (6,24,25), kolinerjik maddelerin emilimi azaltıp intestinal salgıyı artırdığını, antikolinerjik maddelerin ise bağırsak emilimini artırdığını göstermiştir.…”

“…Besinlerin uzaklaştırılmasının bağırsak sekresyonu üzerine etkilerini inceleyen çalışmalar, birçok agonistin ve bakteri toksinlerinin ratlarda, sincaplarda ve domuz yavrularında ince bağırsakta (3,4,24,25), ratlarda ve farelerde kalın bağırsakta (l2, 18) salgıyı artırdığını göstermektedir. Young ve Levin (23) daha ileri giderek açlığın ileumun emilim yapan özelliğini değiştirerek salgıyı doğur-duğunu vurgulamaktadırlar.…”