MECHANISM OF CHLORAMPHENICOL-INDUCED MODULATION OF MOUSE ILEAL MOTILITY

Abstract

The effect of chloramphenicol (CAP) on the intestinal motility of mice was studied. Acute and chronic CAP treatment significantly increased the food transit time. CAP produced concentration-dependent inhibition of motility of the isolated ileum of mice. Prazosin, propranolol, atropine, ouabain and chlorpromazine all failed to modulate or counteract the CAP-induced inhibition of ileal motility. However, naloxone and hexamethonium slightly modified the inhibitory response of CAP. The inhibitory response of CAP was markedly counteracted by cystine, a guanylate cyclase inhibitor. CAP increased the activity of Ca⁺⁺-ATPase in the ileum in all experiments. Our results suggest that the CAP-induced inhibition of the intestinal motility is not mediated through adrenergic, cholinergic and cAMP or through inhibition of the electrogenic pump. Compared to thiamphenicol (TAP), CAP, with a p-NO₂ group in its structure, exhibited more pronounced alteration of both intestinal motility and Ca⁺⁺-ATPase activity. We, therefore, suggest that greater inhibition of ileal motility induced by CAP is possibly a p-NO₂-cGMP-Ca⁺⁺-ATPase-mediated mechanism.