THE INFLUENCE OF A NOVEL PENTADECAPEPTIDE, BPC-157, ON N-G-NITRO-L-ARGININE METHYLESTER AND L-ARGININE EFFECTS ON STOMACH MUCOSA INTEGRITY AND BLOOD-PRESSURE

The known effects of a novel stomach pentadecapeptide BPC157 (10 mu g or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.) -induced gastric lesions (simultaneously applied i.p.) and in blood pr essure maintenance (given i.v.), were investigated in rats challenged with a combination of N-G-nitro-L-arginine methylester (L-NAME) (5 mg/ kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-gen eration and NO precursor, L-arginine (200 mg/kg i.v.) (D-arginine was ineffective). In the gastric lesions assay, NO agents were given 5 min before ethanol injury and BPC 157 medication. Given alone, BPC157 had an antiulcer effect, as did L-arginine, but L-NAME had no effect. L-N AME completely abolished the effect of L-arginine, whereas it only att enuated the effect of BPC 157. After application of the combination of L-NAME + L-arginine, the BPC157 effect was additionally impaired. In blood pressure studies, compared with L-arginine, pentadecapeptide BPC 157 (without effect on basal normal values) had both a mimicking effe ct (impaired L-NAME-blood pressure increase, when applied prophylactic ally and decreased already raised L-NAME values, given at the time of the maximal L-NAME-blood pressure increase (i.e., 10 min after L-NAME) ) and preventive activity (L-arginine-induced moderate blood pressure decrease was prevented by BPC 157 pretreatment). When BPC 157 was give n 10 min after L-NAME + L-arginine combination, which still led to a b lood pressure increase, its previously clear effect (noted in L-NAME t reated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 mu M) as L-a rginine, induced a comparable generation of NO. But, BPC 157 effect co uld not be inhibited by L-NAME, even when L-NAME was given in a tenfol d (100 versus 1000 mu M) higher dose than that needed for inhibition o f the L-arginine effect. NO synthesis was blunted when the pentadecape ptide BPC 157 and L-arginine were combined. In summary, BPC 157 could interfere with the effects of NO on both gastric mucosal integrity and blood pressure maintenance in a specific way, especially with L-argin ine, having a more prominent and/or particularly different effect from that of NO. (C) 1997 Elsevier Science B.V.