BENEFICIAL EFFECT OF A NOVEL PENTADECAPEPTIDE BPC-157 ON GASTRIC-LESIONS INDUCED BY RESTRAINT STRESS, ETHANOL, INDOMETHACIN, AND CAPSAICIN NEUROTOXICITY

Very recently, the integrity of capsaicin somatosensory neurons and th eir protection were suggested to be related to the activity in nocicep tion of a newly discovered 15-amino acid peptide, BPC 157, shown to ha ve strong beneficial effect on intestinal and liver lesions. Therefore , from this viewpoint, we have studied the gastroprotective effect of the pentade-capeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvem ent of sensory neurons in the salutary actions of BPC 157 (10 mu g/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has dif ferential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneous ly) to neonatal animals (age of the 7 days) destroys sensory fibers, w hereas a low dose (500 mu g/kg intraperitoneally) activates neurotrans mitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restrain t, and indomethacin application. In the presence of neurotoxic doses o f capsaicin, the negative influence of capsaicin on restraint, ethanol , or indomethacin lesions consistently affected salutary activity of B PC 157 was applied as a single nanogram-regimen, but the mucosal prote ction was fully reversed when the same dose was used daily. In line wi th the excitatory dose of capsaicin the beneficial effectiveness of BP C 157 appears to be increased as well. Taken together, these data prov ide evidence for complex synergistic interaction between the beneficia l effectiveness of BPC 157 and peptidergic sensory afferent neuron act ivity.