PL EN


Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
1992 | 43 | 4 |

Tytuł artykułu

Studies on gastroprotection induced by capsaicin and papaverine

Treść / Zawartość

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) but the possibility that NO mediates the protective and hyperemic effects of capsaicin and papaverine has been little studied. Using N-nitro-L-arginine (L-NNA), a selective blocker of NO synthase, and L-arginine as a substrate for NO, we investigated the role of NO in protective action of capsaicin and papaverine against ethanol-induced gastric damage and in GBF. Pretreatment with capsaicin (0.1-0.5mg/kg i. g.) or papaverine (0.1-2mg/kg i.g.) reduced dose-dependently the area of ethanol- induced lesions, the LD50 being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous (i. v.) injection of L-NNA (1.2-5 mg/kg), which by itself caused only a small increase in ethanol lesions, reversed dose-dependently the protective and hyperemic effects of capsaicin and papaverine against ethanol-induced damage and attenuated the increase in GBF induced by each of these agents alone. This deleterious effect of L-NNA on the gastric mucosa and the GBF was fully antagonized by L-arginine (200 mg/kg i. v.) but not by D-arginine. L-arginine partly restored the decrease in GBF induced by L-NNA. Pretreatment with indomethacin (5 mg/kg i.p.), which suppressed the generation of PG by 85%, slightly enhaced the mucosal lesions induced by ethanol but failed to affect the fall in GBF induced by this irritant. Gastroprotective and hyperemic effects of capsaicin and papaverine were partly reversed by indomethacin suggesting that endogenous PG are also implicated in these effects. Addition of L-NNA to indomethacin completely eliminated both the protective and hyperemic effects of capsaicin and papaverine. We conclude that both NO and PG contribute to the gastroprotective and hyperemic effects of capsaicin and papaverine on the gastric mucosa.

Wydawca

-

Rocznik

Tom

43

Numer

4

Opis fizyczny

p.309-322,fig.

Twórcy

autor
  • University Medical School, 31-531 Krakow, Grzegorzecka 16, Poland
autor

Bibliografia

  • 1. Holzer P, Sametz W. Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons. Gastroenterology 1986; 91: 975-981.
  • 2. Holzer P, Lippe IT. Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol induced damage of gastric mucosa. Neurosci 1988; 27: 981-987.
  • 3. Hagel J, Renner H, Hirsch M, et al. Gastric cytoprotection by antacids and papaverine in rats. Hepato-Gastroenterol 1982; 29: 271-274.
  • 4. Domschke W, Hagel J, Ruppin H, Kaduk В. Antacid protection of gastric mucosa. Klin Wochenschr 1986; 64: (Suppl VII), 28-31.
  • 5. Szolcsanyi J, Bartho L. Impaired defence mechanism to peptic ulcer in the capsaicin- desensitized rat. In Gastrointestinal Defence Mechanisms, G. Mozsik, O. Hanuinen, T. Javor (eds.). Oxford and Budapest, Pergamon Press and Akademiai Kidao, 1981, pp. 39-51.
  • 6. Buck SH, Burks TF. The neuropharmacology of capsaicin: review of some recent observations. Pharmacol Review 1986; 38: 179-226.
  • 7. Ligumsky M, Rachmilewitz D, Zor V. Papaverine stimulation of prostaglandin E₂ production by cultured rabbit gastric mucosa. Gut 1979; 20: 882-885.
  • 8. Yonei Y, Holzer P, Guth PH. Laparatomy-induced gastric protection against ethanol injury is mediated by capsaicin-sensitive sensory neurons. Gastroenterology 1990; 99: 3-9.
  • 9. Esplugues JV, Whittle BJR, Mancada S. Local opioid-sensitive afferent sensory neurones in the modulation of gastric damage induced by PAF. Br J Pharmacol 1989; 97: 579-585.
  • 10. Holzer P, Pabst MA, Lippe IT. Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the gastric mucosa. Gastroenterology 1989; 1425-1433.
  • 11. Holzer P, Pabst MA, Lippe IT, et al. Afferent nerve-mediated protection against deep mucosal damage in the rat stomach. Gastroenterology 1990; 98: 838-848.
  • 12. Palmer RMJ, Ferriga AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524-526.
  • 13. Mac Naughton WK, Cirino G, Wallace JL. Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach. Life Sei 1989; 45: 1869-1876.
  • 14. Peskar BM, Respondek M, Muller KM, Peskar BA. A role for nitric oxide in capsaicin-induced gastroprotection. Eur J Pharmacol 1991; 198: 113-114.
  • 15. Konturek SJ, Brzozowski T, Drozdowicz D, et al. Nocloprost, a unique prostaglandin E₂ analog with local gastroprotective and ulcer-healing activity. Eur J Pharmacol 1991; 195: 347-357.
  • 16. Holzer P. Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neurosci 1988; 24: 739-768.
  • 17. Holzer P, Peskar BM, Peskar BA, Amann R. Release of calcitonin gene-related peptide induced by capsaicin in the vasculary perfused rat stomach. Neurosci Lett 1990; 180: 195-200.
  • 18. Lippe IT, Pabst MA, Holzer P. Intragastric capsaicin enhances rat gastric elimination and mucosal blood flow by afferent nerve stimulation. Br J Pharmacol 1989; 96: 91-100.
  • 19. Holzer P, Guth PH. Neuropeptide control of rat gastric mucosal blood flow. Circulation Res 1991; 68: 100-105.
  • 20. Evangelista S, Maggi CA, Meli A. Evidence for a role of adrenals in the capsaicin-sensitive “gastric defense mechanism” in rats. Proc Soc Exp Biol Med 1986; 182: 568-569.
  • 21. Guth PH, Leung FW. Physiology of gastric circulation. In Physiology of Gastrointestinal Tract, Johnson LR (ed). New York, Raven Press 1987, pp. 1031-1053.
  • 22. Holm L. Gastric mucosal blood flow and mucosal protection. J Clin Gastroenterol 1989; 10 (Suppl 1): 114-119.
  • 23. Cheung LY. Gastric mucosal blood flow: its measurement and importance in mucosal defense mechanism. J Surg Res 1984; 36: 282-288.
  • 24. Konturek P, Brzozowski T, Konturek SJ, Dembiński A. Role of epidermal growth factor, prostaglandin and sulfhydrys in stress-induced gastric lesions. Gastroenterology 1990; 99: 1607-1615.
  • 25. Whittle BJR, Lopez-Belmonte J, Moncada S. Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol 1990; 99: 607-611.
  • 26. Kitagawa H, Takeda F, Kohei H. Gastric mucosal protective actions of endothelium-derived relaxing factor. Scand J Gastroenterol 1989; 24 (Suppl 162): 131-133.
  • 27. Palmer RMJ, Rees DD, Ashton DS, Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun 1988; 153: 1251-1256.
  • 28. Garrick T, Buack S, Bass P. Gastric motility is a major factor in cold restraint-induced lesion formation in rats. Am J Physiol 1986; 250: G191-G199.
  • 29. Ohno T, Okabe S. Gastric surface epithelial cell damage induced by restraint and water- immersion stress in rats. Protective effects of 16,16-dimethyl prostaglandin E₂. J Clin Gastroenterol 1988; 10 (Suppl 1): S46-S52.
  • 30. Kitagawa H, Takeda F, Kohei H. Effect of endothelium-derived relaxing factor on the gastric lesions induced by HCI in rats. J Pharm Exp Ther 1990; 253: 1133-1137.
  • 31. Moncada S, Radomski N. M., Palmer R. M. Endothelium-derived relaxing factor. Identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem Pharmacol 1988; 37: 2495-2501.
  • 32. Hagoboam CM, Wallace JL. Inhibition of platelet aggregation by capsaicin. An effect unrelated to actions on sensory afferent neurons. Eur J Pharmacol 1991; 202: 129-131.
  • 33. Kvietys PR, Twohig B, Danzell J, Special RD. Ethanol-induced injury to the rat gastric mucosa. Role of neutrophils and xanthine oxidase-derived radicals. Gastroenterology 1990; 98: 909-920.
  • 34. Wallace JL, Keenan CM, Granger DN. Gastric ulceration induced by nonsteroidal antiinflammatory drugs is a neutrophil-dependent process. Am P J Physiol 1990; 259: G 462- G467.
  • 35. Smith SML, Holm-Rutili L, Perry MA et al. Role of neutrophils in haemorrhagic shock- induced gastric mucosal injury in the rat. Gastroenterology 1987; 93: 466-471.
  • 36. Parks DA, Granger DN. Ischemia-induced vascular changes: role of xanthine oxidase and hydroxyl radicals. Am J Physiol 1983; 245: G285-289.
  • 37. Konturek SJ, Brzozowski T, Drozdowicz D, Garlicki J, Beck G. Role of leukotrienes and platelet activating factor in acute gastric mucosal lesions in rats. Eur J Pharmacol 1989; 164: 285-292.
  • 38. Uchida M, Yano S, Watanabe K. The role of capsaicin-sensitive afferent nerves in protective effect of capsaicin against absolute ethanol induced lesions in rats. Jpn J Pharmacol 1991; 55: 279-282.
  • 39. Takeuchi K, Niida H, Matsumoto J, Ueshina K, Okabe S. Gastric motility changes in capsaicin-induced cytoprotection in the rat stomach. Jpn J Pharmacol 1991; 55: 147-155.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

bwmeta1.element.agro-article-afd6e787-7536-47d9-9165-fe83b2a33118
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.