DIARRHEA OF FAMINE AND MALNUTRITION - INVESTIGATIONS USING A RAT MODEL .2. ILEAL HYPERSECRETION INDUCED BY STARVATION

The effects of progressive starvation for up to three days on the basal and secretagogue stimulated secretory functions of the rat ileum were investigated in vitro and in vivo. The secretagogues used included agents acting via cyclic AMP (dibutyryl cyclic AMP, theophylline, forskolin, and PGE2) and those acting via Ca++ (acetylcholine, bethanecol, carbachol, 5-hydroxytryptamine, and A23187). Starving rats for 24 h (day 1) had no effect on the basal electrogenic secretion (measured as the short circuit current, Isc μamps/cm2) or on the stimulated maximum electrogenic secretion (measured as the ΔIsc where ΔIsc = maxIsc - basal Isc). By day 2 of starvation, however, both the basal Isc and the ΔIsc induced by all the secretagogues were significantly greater than in the fed and increased even more on day 3. Replacement of all the chloride ions and inhibition by furosemide indicated that the enhanced secretion was due mainly to chloride ions. Cholinergic stimulation was blocked by atropine, indicating the stimulation was via muscarinic receptors while cholinergic dose - ΔIsc response curves for fed and starved ilea showed significantly increased maximum electrogenic secretory response in the latter but no evidence of any change in the affinity (ED50) of the receptors mediating the response. The basal secretion and the secretory response to acetylcholine in both fed and starved ilea was unaffected by tetrodotoxin, revealing that the enhanced secretory response could be expressed via the muscarinic receptors on the enterocytes without the enteric neural network. Measurement of ileal fluid movement in vivo showed that in fed and day 1 starved rats the basal, unstimulated 'tone' of the ileum was absorptive. On day 2, however, the basal 'tone' had reversed to one of secretion which increased further on day 3. Stimulation of fluid secretion in vivo by bethanecol, carbachol, or PGE2 induced larger increases in the starved ilea by day 2 which increased even further on day 3. Lumenal chloride and bicarbonate concentrations were greater in the starved ileal fluid than in the fed. The studies in rat ileum confirm and extend those on rat jejunum and indicate that starvation creates a hypersensitive small bowel that responds to secretagogues and cholinergic neurotransmitters with a greatly enhanced secretory response.