Capsaicin induces cystatin S-like substances in submandibular saliva of the rat

Irritating dietary substances such as tannin and papain have been reported to alter the morphology of salivary glands and their secretions. Such alter ations can be one line of protection from toxic or irritating substances in food. We investigated the effects of dietary capsaicin (a pungent ingredie nt of hot red pepper) on the rat submandibular gland and its secretions. Se veral groups of animals were offered either control diets or diets containi ng capsaicin (from 0.0001 to 0.1%) for seven days. Higher concentrations su ppressed food consumption for two days, after which only the highest concen tration continued to reduce intake. The relative weight of the salivary gla nds in capsaicin-diet groups increased in a dose-dependent fashion, and new proteins appeared in the submandibular saliva. Chromatographic and electro phoretic properties of these proteins were identical or similar to those of isoproterenol-induced proteins. After affinity chromatography of the new p rotein fraction on a Cm-papain Sepharose 4B column, SDS-electrophoresis of the eluate revealed three major bands (15,500, 16,500, and 28,000 kDa). Hyd rolysis of N-benzoyl-D,L-arginine-p-nitroanilide by papain (a cysteine prot ease) decreased in the presence of the new protein fraction, suggesting tha t these proteins have cystatin-like activity (inhibition of cysteine protea se). Denervation of the glossopharyngeal nerve suppressed induction of thes e proteins. The results suggest that dietary capsaicin induces cystatin S-l ike substances in submandibular saliva by stimulating the reflex are involv ing the glossopharyngeal nerve. These proteins likely facilitate ingestion of diets containing the irritating substance.