ACUTE AND NEONATAL CAPSAICIN TREATMENT INHIBIT JEJUNAL AMINO-ACID-ABSORPTION THROUGH A NA-DEPENDENT MECHANISM()

It has recently been shown that capsaicin inhibits alanine absorption in rat jejunum via mechanisms that involve intestinal capsaicin-sensit ive primary afferent (CSPA) fibers. This study provides further eviden ce that the effect of capsaicin is neurally mediated and demonstrates that CSPA fibers regulate Na+-dependent amino acid absorption. In vivo , basal alanine absorption in rats neonatally treated with capsaicin w as reduced by 35% below control. Furthermore, intraluminal perfusion o f 400 mu M capsaicin reduced jejunal alanine absorption by 31% in sham rats but had no significant effect in rats neonatally treated with ca psaicin. In vitro, capsaicin significantly reduced uptake of alanine a nd proline by jejunal strips but had no effect on uptake of lysine. Te trodotoxin (0.2 mu M) partially blocked the effects of capsaicin but d id not itself affect alanine absorption. Capsaicin reduced unidirectio nal mucosal-toserosal alanine (1 mM) influx by 33%, an effect that bec omes significant after 5 min of preincubation with capsaicin. Neonatal capsaicin treatment reduced basal alanine influx in jejunal strips by 31%; however, preincubation of these strips with capsaicin had no sig nificant effect. Kinetic analysis of alanine steady-state uptake and i nflux by jejunal strips incubated with capsaicin revealed that capsaic in reduced the Na+-dependent component of alanine in influx into intes tinal epithelial cells. Long-term sensory denervation by capsaicin als o decreased the Na+-dependent component of alanine absorption. These d ata suggest that intestinal capsaicin-sensitive primary afferent fiber s regulate Na+-dependent amino acid absorption.