Effect of loperamide on mucosal guanylyl cyclase activity in rat jejunum following Escherichia coli heat-stable toxin-induced fluid accumulation

Loperamide has antidiarrhoeal activities against secretagogues with differe nt mechanisms of action. Besides its opioid-like effect an intestinal motil ity and secretion it might exhibit additional antisecretory properties whic h may not be completely elucidated yet. Direct effects of loperamide on muc osal guanylyl cyclase have never been observed. We therefore investigated t he effect of loperamide on intestinal fluid transport altered by heat-stabl e Escherichia coli enterotoxin which acts by stimulating mucosal guanylyl c yclase. Net fluid movement was determined during a 1 hr incubation period i n ligated jejunal loops of anaesthetised female Wistar rats. Transport rate s of net fluid movement were calculated from the loop contents measured gra vimetrically at the beginning and the end of the experiments. Addition of h eat-stable Escherichia coli enterotoxin to the luminal solution resulted in a net secretion of water which was significantly reversed into net absorpt ion by loperamide. The specific activity of the particulate guanylyl cyclas e was determined in mucosal scrapings of the jejunum without and with the a ddition of heat-stable Escherichia coti enterotoxin and/or loperamide. Addi tions of loperamide of up to 10 mu mol/l did not change guanylyl cyclase ac tivity. We conclude that the effect of loperamide counteracting heat-stable Escherichia coti enterotoxin induced changes of intestinal fluid transport does not involve a direct effect on guanylyl cyclase.