A NOVEL SUBMANDIBULAR-GLAND PEPTIDE PROTECTS AGAINST ENDOTOXIC AND ANAPHYLACTIC SHOCK

Submandibular glands release peptides and proteins that, through exocr ine and endocrine actions, facilitate tissue repair in the oral cavity , gastrointestinal tract, and more distal sites such as liver. It has been shown that salivary gland factors also modulate inflammatory resp onses, because we found that removal of the submandibular glands incre ases the hypotensive responses to endotoxin. From this observation we proposed that these glands contain a factor that regulates cardiovascu lar response to shock. With the use of classical peptide isolation pro cedures, a heptapeptide (TDIFEGG) called submandibular gland peptide T was identified in rat submandibular glands. A synthetic form of this peptide reduced endotoxic shock in sialadenectomized rats by 50% at do ses as low as 1 mu g/kg and prevented allergen-induced hypotension by 90% in rats with intact salivary glands at a dose of 100 mu g/kg. This novel peptide is probably generated from a prohormone, submandibular gland rat 1 protein, a product of the VCSA1 gene. These data indicate that submandibular glands participate in the regulation of systemic ho meostasis.