Effect of neurohumoral control on gastrointestinal absorption of drugs

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In the present study, we tried to investigate the effect of enteric nervous system (ENS) on the drug absorption via passive diffusion mechanism, using phenol red (PR) as a poorly absorbable model compound. To modulate ENS, epinephrine and bethanechol were employed, and their effects were evaluated by the vascular and luminal perfusion study in rat small intestine and the in vitro transport study using the side-by-side diffusion chamber.The infusion of epinephrine increased water absorption. On the contrary, the absorption of PR was significantly reduced by epinephrine and this effect of epinephrine disappeared by removing epinephrine from the vascular perfusate, indicating that the effects of epinephrine should be reversible, In the diffusion chamber experiments using rat jejunum, epinephrine rapidly reduced initial PD and Isc, which would be ascribed to the enhancement of chloride absorption. Rm and the absorption of PR increased and reduced with the addition of epinephrine, respectively. These results suggest that adrenergic nerves might regulate the passive transport of drugs by modulating tight junction, but not by solvent drag.The addition of bethanechol into vascular perfusate converted net water flux to secretion during both the drug infusion and recovery periods, At the beginning of bethanechol infusion, the absorption rate of PR slightly decreased, and then PR absorption increased. Removing bethanechol from the vascular perfusate rapidly reduced the absorption of PR.From these results, it was found that ENS should regulate not only the blood flow, the intestinal motility and the transport of water and/or electrolytes but also the absorption of drug in the intestine.