InflammoPharmacology

, Volume 7, Issue 1, pp 1–14 | Cite as

The pharmacological properties of the novel peptide BPC 157 (PL-10)

Review

Abstract

The reported beneficial effects of the gastric mucosal derived pentadecapeptide BPC 157 (Gly Glu Pro Pro Pro Gly Lys Pro Ala Asp Asp Ala Gly Leu Val, M.W. 1419) on different organ lesions are reviewed. Apart from the effects on various gastrointestinal lesions, the potentially beneficial effect on pancreas, liver injuries, endothelium and heart damage, i.e. dysrhythmias following reoxygenation, and blood pressure, along with effect on experimental acute/chronic inflammation, wound and fracture (pseudoarthrosis) healing are described. It appears that these beneficial effects all together provide a particular network reflecting activity of a special peptidergic defence system. In support of this concept, it appears that there are interactions of this pentadecapeptide with many important systems (namely, dopamine-, NO-, prostaglandin-, somatosensory neurone-systems), that could provide a basis for the observed protective effects. Moreover, since disturbance of these systems’ functions (i.e. dopamine-, NO-, somatosensory neuronal-system) which manifest either over-activity or as inhibition, may contribute to the multiple lesions in different organs. The reported evidence that this pentadecapeptide is able to counteract both their over-action, and their inhibition, may suggest this pentadecapeptide as a new, but most probably essential physiological defence system and that should be further investigated.

Key words:

BPC 157 (PL-10) gastrointestinal lesions acute pancreatitis liver lesions inflammation and pain heart blood pressure behaviour physiological defence system 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Thompson, J., Greeley, G. H. (Jr.), Rayford, P. L. and Townsed, C. M. (Jr.) (1987). Gastrointesti- nal Endocrinology. McGraw-Hill Book Company, New York.Google Scholar
  2. 2.
    Sikiric, P., Petek, M., Rucman, R., etal. (1993). A new gastric juice peptide BPC — an overview of stomach/stress/organoprotection hypothesis and BPC beneficial effects, J. Physiol. (Paris) 87,313–327.CrossRefGoogle Scholar
  3. 3.
    Sikiric, P., Gyires, K., Seiwerth, S., et al. (1993). The effect of pentadecapeptide BPC 157 on inflammatory, non-inflammatory, direct and indirect pain and capsaicin neurotoxicity, Inflammopharmacology 2, 121–127.CrossRefGoogle Scholar
  4. 4.
    Sikiric, P., Banic, M., Brkic, T., et al. (1993). Effects of a novel pentadecapeptide BPC 157 and methylprednisolone in a murine model of inflammatory bowel disease, Gastroenterology 104, 782.Google Scholar
  5. 5.
    Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1993). Hepatoprotective effect of BPC 157, a 15-aminoacid peptide, on liver lesions induced by either restraint stress or bile duct and hepatic artery ligation or CCI4 application. A comparative study with dopamine agonists and somatostatin, Life Sci. 53, PL291-PL296.PubMedCrossRefGoogle Scholar
  6. 6.
    Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1994). The beneficial effect of BPC 157, a 15 aminoacid peptide BPC fragment, on gastric and duodenal lesions induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promotors and gut peptides, Life Sci. 54, PL63-PL68.PubMedCrossRefGoogle Scholar
  7. 7.
    Sikiric, P., Rotkvic, I., Mise, S. et al. (1995). Dopamine agents efficacy in peptic ulcer healing and relapse prevention — a further indication for importance of stomach dopamine in the stress organoprotection concept, in: Neuroendocrinology of Gastrointestinal Ulceration: Hans Selye Symposia on Neuroendocrinology and Stress, Szabo, S., Taché, Y. and Glavin, G. (Eds), Vol. 2, pp. 221–230. Plenum, New York.Google Scholar
  8. 8.
    Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1996). Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats, Digestive Disease Sci. 41, 1518–1526.CrossRefGoogle Scholar
  9. 9.
    Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1996). The beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress, ethanol, indomethacin and capsaicin neurotoxicity, Digestive Disease Sci. 41, 1604–1614.CrossRefGoogle Scholar
  10. 10.
    Sikiric, P., Mazul, B., Seiwerth, S., et al. (1997). Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress, Digestive Disease Sci. 42, 661–671.CrossRefGoogle Scholar
  11. 11.
    Sikiric, P., Mikus, D., Seiwerth, S., et al. (1997). Pentadecapeptide BPC 157, cimetidine, ranitidine, bromocriptine and atropine effect in cysteamine lesions in totally gastrectomized rats. A model study for cytoprotective studies, Digestive Disease Sci. 42, 1029–1037.CrossRefGoogle Scholar
  12. 12.
    Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1997). The influence of a novel pentadecapeptide BPC 157 on NG-nitro-L~arginine methylester and L-arginine effect on stomach mucosal integrity and blood pressure, European J. Pharmacol. 332, 23–33.CrossRefGoogle Scholar
  13. 13.
    Grabarevic, Z., Tisljar, M., Artukovic, B., et al. (1997). The influence of BPC 157 on nitric oxide agonists and antagonist induced lesions in broiler chicks, J. Physiol. (Paris) 91, 139–150.CrossRefGoogle Scholar
  14. 14.
    Seiwerth, S., Sikiric, P., Grabarevic, Z., et al. (1997). BPC 157 effect on healing, J. Physiol. (Paris) 91, 173–178.CrossRefGoogle Scholar
  15. 15.
    Jelovac, N., Sikiric, P., Rucman, R., et al. (1998). A novel pentadecapeptide BPC 157 blocks the stereotypy produced acutely by amphetamine and the developement of haloperidol-induced supersensitivity to amphetamine, Biol. Psych. 43, 511–519.CrossRefGoogle Scholar
  16. 16.
    Konjevoda, P., Nasic, M., Curkovic, T, Sikiric, P., Seiwerth, S. and Stambuk, N. (1998). Effects of BPC 157 on the healing of corneal lesions, in: Uveitis Today, Ohno, S., Aoki, K., Usui, M. and Uchio, E. (Eds), pp. 311–314. Elsevier, Amsterdam.Google Scholar
  17. 17.
    Kalogjera, L., Ries, N., Baudoin, T., Ferencic, Z., Protic, R. and Pegan, B. (1997). Dose dependent protective effect of BPC 157 in capasaicin induced rhinitis in rats, European Arch. Otorhinolaryngol. 254, S9-S11.CrossRefGoogle Scholar
  18. 18.
    Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1997). Pentadecapeptide BPC 157 positively affects both non-steroidal anti-inflammatory agents-induced gastrointestinal lesions and adjuvant arthritis in rats, J. Physiol. (Paris) 91, 113–122.CrossRefGoogle Scholar
  19. 19.
    Sikiric, P., Seiwerth, S., Deskovic, S. et al. (1999). New model of cytoprotection/adaptive cytoprotection in rats: endogenous small irritants, antiulcer agents and indomethacin, European J. Pharmacol. 364,23–31.CrossRefGoogle Scholar
  20. 20.
    Sebecic, B., Nikolic, V., Sikiric, P. et al. (1999). Osteogenic effect of a gastric pentadecapeptide BPC 157, on the healing of segmental bone defect in rabbits. A comparison with bone marrow and autologous cortical bone implantation, Bone 24, 195–202.PubMedCrossRefGoogle Scholar
  21. 21.
    Zoricic, I., Sikiric, P., Seiwerth, S., et al. (1997). Pentadecapeptide BPC 157 beneficially influences the healing of colon-colon anastomoses in rats, in: Cell Injury and Protection in the Gastrointestinal Tract. From basic sciences to clinical perspectives 1996, Mozsik, Gy., Nagy, L., Par, A. and Rainsford, K. D. (Eds), pp. 249–258. Kluwer Academic Publishers, Dordrecht.Google Scholar
  22. 22.
    Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1997). The effect of pentadecapeptide BPC 157, H2 blockers and sucralfate on new vessels and new granulation tissue formation, Gastroenterology 112,291.Google Scholar
  23. 23.
    Sikiric, P., Jadrijevic, S., Seiwerth, S., et al. (1997). Pentadecapeptide BPC 157 reduces esophagojejunal anastomosis-esophageal ulceration in rats, Gastroenterology 112, 219.Google Scholar
  24. 24.
    Bodis, B., Karadi, O., Nagy, L., et al. (1997). Direct cellular effects of some mediators, hormones and growth factor-like agents on denervated (isolated) rat gastric mucosal cells, J. Physiol. (Paris) 91, 183–187.CrossRefGoogle Scholar
  25. 25.
    Bodis, B., Karadi, O., Nagy, L., et al. (1997). Evidence for direct cellular protective effect of PL-10 substances (synthesized parts of body protection compound BPC) and their specificity to gastric mucosal cells, Life Sci. 61, PL 243-PL 248.CrossRefGoogle Scholar
  26. 26.
    Veljaca, M., Pllana, R., Lesch, C. A., Sanchez, B., Chan, K. and Guglietta, A. (1994). Protective effect of BPC 157 on a rat model of colitis, Gastroenterology 106, 789.Google Scholar
  27. 27.
    Veljaca, M., Lech, C. A., Pllana, R., Sanchez, B., Chan, K. and Guglietta, A. (1994). BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats, J. Pharmacol. Exp. Ther. 272,417–422.Google Scholar
  28. 28.
    Veljaca, M, Chan, K. and Guglietta, A. (1995). Digestion of h-EGF, h-TGF α, and BPC 15 in human gastric juice, Gastroenterology 108, 761.CrossRefGoogle Scholar
  29. 29.
    Veljaca, M., Lesch, C. A., Sanchez, B., Low, J. and Guglietta, A. (1995). Protection of BPC-15 on TNBS-induced colitis in rats: possible mechanisms of action, Gastroenterology 108, 936.Google Scholar
  30. 30.
    Bosnjak, Z. J., Graf, B. M. and Sikiric, P. (1994). Protective effects of newly isolated gastric peptide following hypoxic and reoxygenation injury in the isolated guinea pig heart, FASEB J. 8, A 129.Google Scholar
  31. 31.
    Sandor, Z., Vincze, A. and Szabo, S. (1996). The protective effect of a recently isolated gastric peptide in acute and chronic gastroduodenal injury, FASEB J. 10, 171.Google Scholar
  32. 32.
    Sandor, Z., Vincze, A., Jadus, M. R., et al. (1997). The protective effect of newly isolated peptide PL-10 in the iodoacetamide colitis model in rats, Gastroenterology 112, 400.Google Scholar
  33. 33.
    Paré, W. and Kluczynski, J. M. (1994). The effect of new gastric juice peptide BPC on classic stress triad in stress procedure, Exp. Clin. Gastroenterol. 2, 234–236.Google Scholar
  34. 34.
    Erceg, D., Simicevic, V. N., Kolega, M. and Dohoczky, C. (1997). Some aspects of PL-10.1.AK- 15 on the gastrointestinal tract, J. Physiol. (Paris) 91, 179–181.CrossRefGoogle Scholar
  35. 35.
    Szabo, S. and Glavin, G. B. (1990). Hans Selye and the concept of biologic stress. Ulcer pathogenesis as a historical paradigm, Ann. N. Y Acad. Sci. 597, 14–16.PubMedCrossRefGoogle Scholar
  36. 36.
    Selye, H. (1936). A syndrome produced by diverse noxious agents, Nature 138, 32.Google Scholar
  37. 37.
    Robert, A. (1979). Cytoprotection by prostaglandins, Gastroenterology 77, 761–767.PubMedGoogle Scholar
  38. 38.
    Moneada, S., Palmer, R. M. J. and Higgs, E. A. (1991). Nitric oxide: physiology, pathophysiology, and pharmacology, Pharmacol. Rev. 43, 109–142.Google Scholar
  39. 39.
    Whittle, B. J. R., Boughton-Smith, N. K. and Moneada, S. (1992). Biosynthesis and role of the endothelium-derived vasodilator, nitric oxide in gastric mucosa, Ann. N. Y Acad. Sci. 664, 126–139.PubMedCrossRefGoogle Scholar
  40. 40.
    Holzer, P. (1991). Peptidergic sensory neurons in the control of vascular functions: Mechanisms and significance in the cutaneous and splanchnic vascular beds, Rev. Physiol. Biochem. Pharmacol. 121,49–146.CrossRefGoogle Scholar
  41. 41.
    Szabo, S., Trier, T. S., Brown, A. and Schnoor, J. (1985). Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat, Gastroenterology 88, 228–236.PubMedGoogle Scholar
  42. 42.
    Szabo, S. and Usadel, K. H. (1982). Cytoprotection-organoprotection by somatostatin: gastric and hepatic lesions, Experientia. 38, 254–256.PubMedCrossRefGoogle Scholar
  43. 43.
    Szabo, S. (1986). Experimental basis for a role for sulfhydryls and dopamine in ulcerogenesis: a primer for cytoprotection-organoprotection, Klin-Wochenschr. 64 (suppl. 7), 116–122.PubMedGoogle Scholar
  44. 44.
    Geokas, M. C, Baltaxe, H. A., Banks, P. A., Silva, J. and Frey, C. F. (1985). Acute pancreatitis, Ann. Int. Med. 103, 86–100.PubMedGoogle Scholar
  45. 45.
    Par, A. (1992). Free radical mechanisms in gastrointestinal and liver diseases. A review, Exp. Clin. Gastroenterol. 2, 162–173.Google Scholar
  46. 46.
    Slater, T. F., Cheeseman, K. H., Davies, M. J., Proudfoot, K. and Sharma, O. P. (1985). Mechanisms of protection against free-radical-mediated liver cell injury, in: Free radicals in liver injury, Slater, T. F., Cheeseman, K. H. and Davies, M. J. (Eds), pp. 197–205. IRL Press, Oxford, Washington.Google Scholar
  47. 47.
    Damas, J. and Deflandre, E. (1984). The mechanism of anti-inflammatory effect of turpentine in the rat, Naunyn-Schmiedeberg’s Arch. Pharmacol. 327, 143–147.CrossRefGoogle Scholar
  48. 48.
    Willoughby, S. G., Hopps, R. M. and Johnson, N. W. (1986). Changes in the epithelial proliferation of rat or oral mucosa in response to acute inflammation induced by turpentine, Archs Oral Biol. 31, 193–199.CrossRefGoogle Scholar
  49. 49.
    Winter, C. A., Risley, E. A. and Nuss, G. W. (1962). Carrageenin-induced oedema in hind paw of the rat as an assay for antiinflammatory drugs, Proc. Soc. Exp. Biol. Med. 111, 544–547.PubMedGoogle Scholar
  50. 50.
    Gyires, K., Furst, S., Miklya, I., Budavari, I. and Knoll, J. (1985). Analysis of the analgetic and anti-inflammatory effects or rimazolium, a pyrimido-pyrimidine derivate, compared with that of prostaglandin synthesis inhibitors and morphine, Drugs Exptl Clin. Res. 11, 495–500.Google Scholar
  51. 51.
    Brkic, T., Banic, M., Anic, B., Grabarevic, Z., Rotkvic, I., Artukovic, B., Duvnjak, M., Sikiric, P., Troskot, B., Hernandez, D. E. (1992). A model of inflammatory bowel disease induced by 2,4-dinitrofluorbenzene in previously sensitized BALB-c mice, Scand. J. Gastroenterol. 27, 184–188.PubMedGoogle Scholar
  52. 52.
    Klagsburn, M. and Folkman, J. (1991). Angiogenesis, in: Peptide Growth Factors and their Receptors II, Sporn, M. B. and Roberts, A. B. (Eds), pp. 549–586. Springer-Verlag, New York.Google Scholar
  53. 53.
    Klinge, B., Lehto-Axtelius, D., Akerman, M. and Hakanson, R. (1985). Structure of calvaria after gastrectomy. An experimental study in the rat, Scand. J. Gastroenterol. 30, 952–957.Google Scholar
  54. 54.
    Kobayashi, S., Takahashi, C., Kuroda, T., Sugenoya, A., Iida, F. and Katoh, K. (1994). Calcium regulating hormones and bone mineral content in patients after subtotal gastrectomy, Surg Today. 24, 295–298.PubMedCrossRefGoogle Scholar
  55. 55.
    Masuda, Y., Murai, S., Saito, H., et al. (1991). The enhancement of the hypomotility induced by small doses of haloperidol in the phase of dopaminergic supersensitivity in mice, Neuropharma- cology 30, 35–40.CrossRefGoogle Scholar
  56. 56.
    Adams, J. D. and Odunze, I. N. (1991). Commentary. Biochemical mechanisms of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity, Biochem. Pharmacol. 41, 1099–1105.PubMedCrossRefGoogle Scholar

Copyright information

© VSP 1999

Authors and Affiliations

  1. 1.Department of Pharmacology, Medical FacultyUniversity of ZagrebHR ZagrebCroatia

Personalised recommendations