In previous work, we demonstrated that dehydroleucodine (DhL), a lactone isolated from Artemisia douglasiana Besser, prevents gastroduodenal damage induced by absolute ethanol (EtOH). The present study examined the effects of DhL – applied alone or before EtOH – on gastroduodenal cells containing 5-hydroxytryptamine (5-HT), to clarify the mechanism of action of the drug. Mice were divided into four groups: (I) control; (II) DhL; (III) EtOH, and (IV) DhL + EtOH. Stomachs and duodena were studied by immunohistochemistry and image analysis. EtOH decreased the immunopositive cell number and the area occupied by these cells. This effect was prevented by DhL. DhL alone did not affect the gastric immunopositive cell number and area. Duodena treated only with DhL exhibited a reduction of immunopositive cell number, but no change in area was observed. We propose that the drug probably inhibits the release of the inflammatory mediator 5-HT from endocrine cells, acting as a ‘cell stabilizer’ in response to injury.

Keywords:
5-Hydroxytryptamine, Immunohistochemistry, Image analysis, Ethanol, Ulcer, Mouse
1.
Briejer, M.R., L.M.A. Akkermans, R.A. Lefebvre, J.A.J. Schuurkes (1995a) Novel 5 HT2 like receptor mediates neurogenic relaxation of the guinea-pig proximal colon. Eur J Pharmacol 279: 123–133.
2.
Briejer, M.R., L.M.A. Akkermans, J.A.J. Schuurkes (1995b) Gastrointestinal prokinetic benzamides: The pharmacology underlying stimulation of motility. Pharmacol Rev 47: 631–651.
3.
Cho, C.H. (1994) The role of endogenous ulcerogenic mediators in the pathogenesis of peptic ulcer. Life Sci 55: 1521–1535.
4.
Ciancio, M.J., E.B. Chang (1992) Epithelial secretory response to inflammation; in Stead, R.H., M.H. Perdue, H. Cooke, D.W. Powell, K.E. Barrets (eds): Neuro-Immuno-Physiology of the Gastrointestinal Mucosa. New York, Ann NY Acad Sci, vol 664, pp 210–221.
5.
Cooke, H. (1986) Neurobiology of the intestinal mucosa. Gastroenterology 90: 1057–1081.
6.
Elias, J.M., M. Margiotta, D. Gaborc (1989) Sensitivity and detection efficiency on the peroxidase-antiperoxidase (PAP), avidin-biotin peroxidase complex (ABC), and peroxidase-labeled avidin-biotin (LAB) methods. Am J Clin Pathol 92: 62–67.
7.
Farrae, A.J., M. Colombo, I. Alvarez, G.B. Glavin (1995) Some novel 5-hydroxytryptamine1A (5-HT1A) receptor agonists reduce gastric acid and pepsin secretion, reduce experimental gastric mucosal injury and enhance gastric mucus in rats. J Pharmacol Exp Ther 272: 832–837.
8.
Gidener, S., K.J. LePard, R. Stephens (1995) 8-OH-DPAT stimulates gastric acid secretion through a vagal-independent, adrenal-mediated mechanism. Eur J Pharmacol 254: 19–24.
9.
Giordano, O.S., E. Guerreiro, M.J. Pestchanker, J. Guzmán, D. Pastor, T. Guardia (1990) The gastric cytoprotective effect of several sesquiterpene lactons. J Nat Prod 53: 803–809.
10.
Glavin, G.B., A.M. Hall (1991) Experimental gastric ulcer: Recent data suggest potential new therapeutic strategies. Asia Pacif J Pharmacol 6: 331–339.
11.
Graf, S., S.K. Sarna (1996) 5-HT-induced jejunal motor activity: Enteric locus of action and receptor subtypes. Am J Physiol 270: G992–G1000.
12.
Grundy, D., L.A. Blackshaw, K. Hillsley (1994) Role of 5-hydroxytryptamine in gastrointestinal chemosensitivity. Dig Dis Sci 39: 445–475.
13.
Guardia, T., J.A. Guzmán, A. Juárez, E. Guerreiro, O. Giordano (1995) Acción antiinflamatoria de dehidroleucodina (DhL). Acta Physiol Pharmacol Ther Latinoam 45: 226.
14.
Haga, N., A. Mizumoto, M. Satoh, E. Mochiki, F. Mizusawa, K. Ohshima, Z. Itoh (1996) Role of endogenous 5-hydroxytryptamine in the regulation of gastric contractions by motilin in dogs. Am J Physiol 270: G20–G28.
15.
Hegde, S., R. Eglen (1996) Peripheral 5-HT4 receptors. FASEB J 10: 1398–1407.
16.
Juarez, A.D., T. Guardia, J. Guzmán, O.S. Giordano, E. Guerreiro (1996) Antiinflammatory activity of dehydroleucodine (DhL) in rats. Acta Physiol Pharmacol Ther Latinoam 46: 194.
17.
Lepard, K.J., J. Chi, J.R. Mohammed, S. Gidener, R.L. Stephens (1996) Gastric antisecretory effect of serotonin: Quantitation of release and site of action. Am J Physiol 271: E669–E677.
18.
Matsuo, T., H. Mori, Y. Nishimura, T. Maeda, J. Nakagawa, A. Obashi (1995) Quantification of immunohistochemistry using an image analyser: Correlation with hormone concentrations in pituitary adenomas. Histochem J 27: 989–996.
19.
Matsuyama, S., H. Sakiyama, K. Nei, C. Tanaka (1996) Identification of putative 5-hydroxytryptamine4 (5-HT4) receptors in guinea pig stomach: The effect of TKS159, a novel agonist, on gastric motility and acetylcholine release. J Pharmacol Exp Ther 276: 989–995.
20.
Nagakura, Y., T. Kamato, A. Nishida, H. Ito, M. Yamano, K. Miyata (1996) Characterization of 5-hydroxytryptamine (5-HT) receptor subtypes influencing colonic motility in conscious dogs. Arch Pharmacol 353: 489–498.
21.
Ogle, C.W., S.C.G. Hui (1995) The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats. Experientia 51: 786–789.
22.
Penissi, A.B., J. Guzmán, T. Fogal, R.S. Piezzi (1998) Gastroduodenal mucosal protection induced by dehydroleucodine: Mucus secretion and role of monoamines. Dig Dis Sci 43: 791–798.
23.
Piezzi, R.S., J.A. Guzmán, T. Guardia, M.J. Pestchanker, E. Guerreiro, O.S. Giordano (1992) Dehydroleucodine prevents ethanol-induced necrosis in the rat gastric mucosa: A histological study. Micr Electr Biol Cel 16: 45–56.
24.
Piezzi, R.S., J.A. Guzmán, T. Guardia, M.J. Pestchanker, E. Guerreiro, O.S. Giordano (1995) Dehydroleucodine prevents ethanol-induced necrosis in the mice duodenal mucosa: A histological study: Biocell 19: 27–33.
25.
Wade, P.R., J. Chen, B. Jaffe, I.S. Kassem, R.D. Blakely, M.D. Gershon (1996) Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci 16: 2352–2364.
© 2000 S. Karger AG, Basel
2000
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