Effect of tetrodotoxin on cholinergic agonist-mediated colonic electrolyte transport

Muscarinic cholinergic agonists stimulate electrolyte secretion in the intestine; nicotinic agonists augment absorption. Recent studies in rabbit ileum suggest that nicotinic but not muscarinic agonists act via an intermediary neurotransmitter. These in vitro studies in rat colon were performed to determine whether tetrodotoxin (TTX), a potent neurotoxin, inhibits cholinergic agonist-induced changes in electrolyte transport. TTX did not significantly alter basal ion transport or the ion transport changes produced by either theophylline or bethanechol, a muscarinic agonist. At a concentration of 1 mM carbachol, a mixed muscarinic-nicotinic agonist, had no apparent effect on ion transport but in the presence of TTX significantly decreased net sodium absorption, similar to the effect produced by 1 microM carbachol alone. These results are consistent with the concept that in low concentrations carbachol acts predominantly as a muscarinic agonist; in high concentrations carbachol exhibits both muscarinic and nicotinic properties that are equivalent. We conclude that muscarinic agonists alter electrolyte transport by acting directly on the enterocyte and that nicotinic agonists act indirectly by stimulating the release of an intermediary neurotransmitter.