Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence

被引：27

作者：

Brzozowski T. ^{[1
]}

Konturek P.C. ^{[2
]}

Drozdowicz D. ^{[1
]}

Konturek S.J. ^{[1
]}

Pawlik M. ^{[1
]}

Sliwowski Z. ^{[1
]}

Pawlik W.W. ^{[1
]}

Hahn E.G. ^{[2
]}

机构：

[1] Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow

[2] Department of Medicine I, University Erlangen-Nuremberg, 91054 Erlangen

来源：

InflammoPharmacology | 2005年 / 13卷 / 1-3期

关键词：

Calcitonin-gene-related peptide; Ethanol; Gastric mucosal blood flow; Gastroprotection; Ghrelin; Nitric oxide; Stress;

D O I：

10.1163/156856005774423971

中图分类号：

学科分类号：

摘要：

Ghrelin, identified in the gastric mucosa, has been involved in the control of food intake and growth hormone (GH) release, but whether this hormone influences the gastric secretion and gastric mucosal integrity has been little elucidated. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without suppression of nitric oxide (NO)-synthase or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by the H2-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. In addition, the gastric mucosal expression of mRNA for CGRP, the most potent neuropeptide released from the sensory afferent nerves, was analyzed in rats exposed to WRS with or without ghrelin pre-treatment. Ghrelin (5-80 μg/kg i.p. or 0.6-5 μg/kg i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS. This protective effect was accompanied by a significant rise in the gastric mucosal blood flow (GBF), luminal NO concentration and plasma ghrelin and gastrin levels. Ghrelin-induced protection was abolished by vagotomy and significantly attenuated by L-NNA and deactivation of afferent nerves with neurotoxic dose of capsaicin. The signal for CGRP mRNA was significantly increased in gastric mucosa exposed to WRS as compared to that in the intact gastric mucosa and this was further enhanced in animals treated with ghrelin. We conclude that central and peripheral ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol or WRS, and these effects depend upon vagal activity and hyperemia mediated by the NOS-NO system and CGRP released from sensory afferent nerves. © VSP 2005.

引用

页码：45 / 62

页数：17

共 35 条

[11]

Heineman A., Jocic M., Peskar B.M., Et al., CCK-evoked hyperemia in rat gastric mucosa in involves neural mechanisms and nitric oxide, Am. J. Physiol., 270, pp. 253-258, (1996)

[12]

Holzer P., Livingston E.H., Saria A., Et al., Sensory nerves mediate protective vasodilation in the rat gastric mucosa, Am. J. Physiol., 260, (1991)

[13]

Kojima M., Hosoda H., Date Y., Et al., Ghrelin is a growth-hormone-releasing acylated peptide from stomach, Nature, 402, pp. 656-660, (1999)

[14]

Kojima M., Kangawa K., Ghrelin, an orexigenic signaling molecule from the gastrointestinal tract, Curr. Opin. Pharmacol., 2, pp. 665-668, (2002)

[15]

Konturek P.C., Brzozowski T., Meixner H., Et al., Central and peripheral neural aspects of gastroprotective and ulcer healing effects of lipopolysaccharides, J. Physiol. Pharmacol., 52, pp. 611-623, (2001)

[16]

Konturek P.C., Brzozowski T., Sulekova Z., Et al., Role of leptin in ulcer healing, Eur. J. Pharmacol., 414, pp. 87-97, (2001)

[17]

Konturek P.C., Brzozowski T., Pajdo R., Et al., Ghrelin - A new gastroprotective factor in the gastric mucosa, J. Physiol. Pharmacol., 55, pp. 325-336, (2004)

[18]

Konturek P.C., Nikiforuk A., Brzozowski T., Et al., Effect of N-alpha-methyl histamine on ulcer healing in rats, Inflamm. Res., 53, SUPPL. 1, (2004)

[19]

Konturek S.J., Brzozowski T., Dembinski A., Et al., Interaction of growth hormone-releasing factor and somatostatin on ulcer healing and mucosal growth in rats: Role of gastrin and epidermal growth factor, Digestion, 41, pp. 121-128, (1988)

[20]

Konturek S.J., Brzozowski T., Bielasski W., Et al., Role of endogenous gastrin in gastroprotection, Eur. J. Pharmacol., 278, pp. 203-212, (1995)

← 1 2 3 4 →