EFFECTS OF NEUROPEPTIDE-Y AND SUBSTANCE-P ON ANTIGEN-INDUCED ION SECRETION IN RAT JEJUNUM

We previously described a model of intestinal hypersensitivity in whic h isolated gut segments from sensitized rats demonstrated a rapid epit helial secretory response to luminal antigen that was mediated by muco sal mast cells and capsaicin-sensitive nerves. In this study, we exami ned the ability of the inhibitory neuropeptide, neuropeptide Y (NPY), to diminish the antigen-induced secretory response. Rats were sensitiz ed to egg albumin (EA), and 12-14 days later, jejunal tissue was excis ed and mounted in Ussing chambers. NPY inhibited the short-circuit cur rent (I-sc) increase and Cl- secretion evoked by addition of EA to the luminal side of the tissue; neural blockade with tetrodotoxin (TTX) h ad a similar inhibitory effect. In contrast, NPY was much less effecti ve, and TTX was completely ineffective, on the response to serosal ant igen. Additional experiments examined the cell target for NPY action. NPY and TTX almost abolished the I-sc response to electrical transmura l stimulation of enteric nerves, suggesting a possible neural site of action. In addition, NPY significantly reduced baseline I-sc; this inh ibition involved both TTX-dependent and TTX-independent components. Be cause nerves were previously shown to facilitate antigen uptake and su bstance P was implicated in the response to only luminal antigen, we p ostulated that NPY was inhibiting nerves that facilitate antigen trans port from the lumen to effector cells in the lamina propria. We theref ore examined the effect of exogenous substance P added after NPY inhib ition. Substance P restored the luminal antigen-induced secretory resp onse to pretreatment values. We conclude that the neuropeptides play a significant role in immunophysiology by acting at neural and epitheli al sites in the intestinal mucosa.