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.