CHOLERA-INDUCED MUCIN SECRETION FROM RAT INTESTINE - LACK OF EFFECT OF CAMP, CYCLOHEXIMIDE, VIP, AND COLCHICINE

Purified cholera enterotoxin (20-50 .mu.g) and dialyzed cholera filtrate (50-125 mg) increased net glycoprotein synthetic and secretory rates in rat intestinal epithelium. Specific goblet cell mucin secretion was increased 5- to 10-fold. However, other agents that increase intestinal cAMP and accelerate glycoprotein synthesis did not enhance mucin secretion. This was true for dibutyryl cAMP (10-3 and 10-2 M) with or without theophylline (10-3 M). Hyperosmotic minnitol (450 mosmol/l), which increases fluid secretion but does not affect cAMP, and vasoactive intestinal peptide (2 .times. 10-7 M), which increases both fluid secretion and cAMP, both failed to increase mucin secretion, implying that fluid "washout" of mucin adherent to the mucosal surface is not responsible for cholera-induced mucin secretion. Cycloheximide, and inhibitor of cholera diarrhea in vivo (20 mg/kg) or in vitro (1 mM), effectively abolished [3H] leucine incorporation into protein but did not affect cholera induced mucin secretion. Colchicine (10-50 mg/kg) given to block microtubule assembly was similarly without effect on mucin secretion. There apparently is a dissociation of electrolyte/fluid and mucin secretory processes. The widely accepted notion that all cholera effects are mediated via the well-known adhenylate cyclase-cAMP mechanism is questioned.