Anticholeraic effect of methylated casein in rat jejunum

To explore the antisecretory effect of methylated casein (MC) cholera toxin was placed in isolated jejunal loops, and in vivo water fluxes were measured 3 h later in the presence or absence of MC. Secretion was observed in the loops filled with Ringer's solution only, but net absorption was observed in all 10 loops to which MC was added. Its actions was evident within 20 min, and was exerted directly on the luminal side of the epithelium. This response was dose-dependent and the antisecretory effect vanished after boiling MC and after ultrafiltration. In vitro, the antisecretory effect of MC consisted of reversing net Na and Cl fluxes from secretion to absorption (delta JNanet = 6.18 +/- 1.25 and delta JClnet = 5.10 +/- 1.66 microEq . h-1 . cm-2). This change was due to the enhancement of mucosal to serosal flux. Transepithelial potential difference and tissue conductance did not alter. Interestingly, MC did not interfere with intestinal function in the absence of stimulation by cholera toxin. In the presence of cholera toxin, MC and glucose both stimulated ionic absorption by different mechanisms, MC stimulating neutral NaCl absorption, and glucose stimulating electrogenic Na absorption. MC did not alter basal adenylate cyclase activity but it inhibited the cholera toxin-stimulated increase in activity. The present results indicate that methylated casein inhibits water and electrolyte secretion induced by cholera toxin in rat jejunum. Its availability, low cost, and curative effect from the luminal side constitute compelling indications for further investigation.