Sikirić P, Seiwerth S, Grabarević Z, Rucman R, Petek M, Jagić V, Turković B, Rotkvić I, Mise S, Zoricić I, Konjevoda P, Perović D, Jurina L, Separović J, Hanzevacki M, Artuković B, Bratulić M, Tisljar M, Gjurasin M, Miklić P, Stancić-Rokotov D, Slobodnjak Z, Jelovac N, Marović A
Center for Digestive Diseases, Medical Faculty, University of Zagreb, Croatia.
Eur J Pharmacol. 1997 Jul 30;332(1):23-33. doi: 10.1016/s0014-2999(97)01033-9.
The known effects of a novel stomach pentadecapeptide BPC157 (10 microg or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.)-induced gastric lesions (simultaneously applied i.p.) and in blood pressure 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)-generation 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-NAME completely abolished the effect of L-arginine, whereas it only attenuated 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 effect (impaired L-NAME-blood pressure increase, when applied prophylactically 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 given 10 min after L-NAME + L-arginine combination, which still led to a blood pressure increase, its previously clear effect (noted in L-NAME treated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 microM) as L-arginine, induced a comparable generation of NO. But, BPC 157 effect could not be inhibited by L-NAME, even when L-NAME was given in a tenfold (100 versus 1000 microM) higher dose than that needed for inhibition of the L-arginine effect. NO synthesis was blunted when the pentadecapeptide 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-arginine, having a more prominent and/or particularly different effect from that of NO.
研究了新型胃十五肽BPC157（10微克或10纳克/千克）的已知作用，即其对乙醇（96%，灌胃）诱导的胃损伤（同时腹腔注射）的有益作用以及对维持血压（静脉注射）的作用，实验对象为用N（G）-硝基-L-精氨酸甲酯（L-NAME）（5毫克/千克静脉注射）、内皮一氧化氮（NO）生成的竞争性抑制剂和NO前体L-精氨酸（200毫克/千克静脉注射）（D-精氨酸无效）联合处理的大鼠。在胃损伤实验中，在乙醇损伤和BPC 157给药前5分钟给予NO制剂。单独使用时，BPC157具有抗溃疡作用，L-精氨酸也有此作用，但L-NAME无作用。L-NAME完全消除了L-精氨酸的作用，而仅减弱了BPC 157的作用。应用L-NAME + L-精氨酸组合后，BPC157的作用进一步受损。在血压研究中，与L-精氨酸相比，十五肽BPC 157（对基础正常值无影响）具有模拟作用（预防性应用时可减弱L-NAME引起的血压升高，并降低L-NAME血压升高最大值时（即L-NAME注射后10分钟）已升高的L-NAME值）和预防作用（BPC 157预处理可预防L-精氨酸引起的中度血压下降）。当在L-NAME + L-精氨酸组合后10分钟给予BPC 157时，此时仍会导致血压升高，其先前明显的作用（在L-NAME处理的大鼠中观察到）消失。在体外，在大鼠胃组织匀浆的胃黏膜中，与L-精氨酸相同剂量（100微摩尔）的BPC 157可诱导产生相当量的NO。但是，即使L-NAME的剂量比抑制L-精氨酸作用所需剂量高10倍（100对1000微摩尔），L-NAME也不能抑制BPC 157的作用。当十五肽BPC 157和L-精氨酸联合使用时，NO合成受到抑制。总之，BPC 157可以以特定方式干扰NO对胃黏膜完整性和血压维持的作用，特别是与L-精氨酸相比，其作用更为突出和/或特别不同。
