Biol. Pharm. Bull. 30(3) 547—551 (2007)

pound responsible for the pungent character of various hot peppers (Capsicum), and it is famous for its pungent taste, burning sensation, and various effects on body temperature and gastric acid secretion. These features of capsaicin are considered to be generated by capsaicin associating with the capsaicin receptor, or the transient receptor potential cation channel of vanilloid type 1 (TRPV1) on the nerve endings of afferent neurons. Since it is reported that TRPV1 regulates cation influx in nerve cells and that Ca permeability in those cells largely depends on TRPV1 activity, capsaicin is thought to induce an extracellular Ca influx into nerve cells by associating with TRPV1, and thereby it stimulates afferent neurons to generate the characteristic sensations. It is reported that the capsaicin-induced Ca influx via TRPV1 prompts the afferent neurons innervating the gastrointestinal tract to release neuropeptides such as calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP). Since these neuropeptides are involved in the regulation and/or maintenance of various gastrointestinal functions by stimulating mesenteric blood flow, preventing mucosal injury, and controlling electrolyte secretion, capsaicin in savory cuisine is likely to vary the gastrointestinal conditions, and as a result, it may alter the intestinal absorption processes of orally administered medicines. In fact, capsaicin is suggested to affect mucosal integrity, peristaltic activity, and the absorption/secretion of various electrolytes in the gastrointestinal tract. In addition, it was demonstrated that capsaicin decreased intestinal alanine absorption by stimulating afferent neurons to release CGRP and VIP. Recently, it was suggested that TRPV1 is expressed not only in nerve cells, but also in gastric mucosal tissues and intestinal epithelia. As capsaicin associates with TRPV1, thus increasing Ca influx, it may alter the intracellular Ca concentration in these cells. If this is the case, capsaicin probably affects the intestinal drug absorption processes in a direct manner. This is because changes in the intracellular Ca concentration alter the paracellular permeability of intestinal epithelia by modifying the integrity of the epithelial tight junction. In addition to the paracellular pathway of the intestinal drug absorption processes, capsaicin may affect the transcellular pathway of the process, since the intracellular Ca concentration is related to the drug transporting activity of various transporters including H /peptide co-transporter 1 (PEPT1). It is therefore suggested with these findings and considerations that capsaicin has an impact on the intestinal drug absorption processes. However, little is known about the effect of capsaicin on intestinal drug absorption. To clarify whether capsaicin affects intestinal drug absorption, we examined the intestinal drug absorption profiles of rats in the presence and absence of capsaicin in this study, in which we used cephalexin as a model drug since its absorption processes have been thoroughly studied. We also examined whether TRPV1 plays an important role in capsaicin’s effect, and further elucidated an underlying mechanism of the capsaicin-induced alteration of intestinal cephalexin absorption.