Effects of hexarelin against acid-independent and acid-dependent ulcerogens in the rat

Sibilia, V.; Torsello, Antonio; Pagani, F.; Rapetti, D.; Lattuada, N.; Locatelli, Vittorio; Bulgarelli, Ilaria; Guidobono, F.; Netti, C.

doi:10.1016/j.peptides.2004.08.001

Cited by 15 publications

(18 citation statements)

References 33 publications

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“…These findings are in keeping with previous data showing protective effects of ghrelin against other models of gastric injury, including ethanol, stress and ischemia [13,21,22,43] , and confirm that ghrelin is a gastroprotective factor in the rat stomach. The partial efficacy (43% inhibition) displayed by the peptide in the present study is in line with literature data, which showed maximal effects of ghrelin in intact animals, ranging from 20 to 70%, according to the experimental assay [13,18,19,22,29] .…”

Section: Discussionsupporting

confidence: 92%

“…The lack of ulcerogenic effects of [ D -Lys 3 ]-GHRP-6 by itself in basal conditions or under HCl challenge confirms previous studies [22,43] , which showed that this antagonist by itself did not modify ethanol-or ischemia/reperfusion-induced gastric lesions. These data would suggest that endogenous ghrelin does not play a major role in the maintenance of gastric mucosal defense under physiological conditions or under exposure to ulcerogenic stimuli.…”

Section: Discussionsupporting

confidence: 88%

“…The effect of ghrelin was totally antagonized by [ DLys 3 ]-GHRP-6, a compound which is considered the reference antagonist of GHS-R 1a in functional studies [11,26,43,45] , indicating that the GHS-R 1a is involved in the gastroprotective activity of ghrelin. The lack of ulcerogenic effects of [ D -Lys 3 ]-GHRP-6 by itself in basal conditions or under HCl challenge confirms previous studies [22,43] , which showed that this antagonist by itself did not modify ethanol-or ischemia/reperfusion-induced gastric lesions.…”

Section: Discussionmentioning

confidence: 99%

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Histamine H<sub>3</sub> Receptors Are Involved in the Protective Effect of Ghrelin against HCl-Induced Gastric Damage in Rats

et al. 2010

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In the present study, the effects of ghrelin against the gastric damage induced by intragastric administration of 0.6 N HCl and the involvement of histamine H₃ receptors (H₃Rs) were investigated in conscious rats with selective H₃R ligands. Intraperitoneal (i.p.) injection of ghrelin (40 µg/kg) significantly reduced (43%) the gastric lesions caused by concentrated acid. The effect of ghrelin was prevented by prior administration of the ghrelin receptor antagonist [D-Lys³]-GHRP-6 (100 µg/kg i.p.) and by subcutaneous (s.c.) injection of the nonimidazole H₃R antagonist UCL2138 (30 mg/kg). The selective H₃R agonist immethridine (30 mg/kg s.c.) significantly inhibited (64.60%) the gastric lesions induced by 0.6 N HCl. The effect of immethridine was prevented by prior administration of UCL2138 (30 mg/kg s.c.), but not by [D-Lys³]-GHRP-6 (100 µg/kg i.p.). Neither [D-Lys³]-GHRP-6 nor UCL2138 modified HCl-induced gastric damage per se. These data enlarge previous studies showing protective effects of ghrelin against ulcerogenic stimuli; in addition, they clearly indicate that ghrelin-induced gastroprotection involves the release of histamine, which enhances gastric mucosal defense through the activation of histamine H₃Rs.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Histamine H<sub>3</sub> Receptors Are Involved in the Protective Effect of Ghrelin against HCl-Induced Gastric Damage in Rats

et al. 2010

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“…However, factors other than endogenous PGs, possibly NO, or sensory neuropeptides such as CGRP could also contribute to this effect, and therefore, their involvement in ulcer healing activity of ghrelin and orexin-A should be addressed in future studies. The finding that COX-1 and COX-2 inhibitors greatly attenuated the ulcer healing activity of ghrelin, is in keeping with the observation that ghrelin is ineffective in the protection against indomethacin-induced gastric ulcers [41], where the mucosal generation of PGE 2 is greatly suppressed.…”

Section: Insight Of Cox-pg System To Ghrelin-induced Acceleration Of supporting

confidence: 82%

Involvement of Orexigenic Peptides in the Mechanism of Gastric Mucosal Integrity and Healing of Chronic Gastric Ulcers

Szlachcic¹,

Brzozowski²,

Majka³

et al. 2010

CPD

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Orexigenic peptides are group of endocrine hormones exerting a pleiotropic influence on many physiological functions including regulation of the feeding behaviour and energy expenditure, release of growth hormone (GH) and inotropic effects on the heart. Some of these peptides such as ghrelin, originally identified in the gastric mucosa, has been involved not only in control of food intake and growth hormone release but also exerts the immunomodulatory and anti-inflammatory properties. This review summarizes the recent attempts to prove the concept that orexigenic peptides such as ghrelin, orexin-A and obestatin besides playing an important role in the mechanism of food intake, exhibit a potent gastroprotective action against the formation of acute gastric mucosal injury induced by various ulcerogens. This protective effect depends upon vagal activity and hyperemia mediated by NOS/NO and COX/PG systems and CGRP released from sensory afferent nerves. In addition, the appetite peptides such as ghrelin and orexin-A are implicated in the mechanism of the healing of preexisting gastric ulcers due to an activation of specific GHS-R1a and OX-R1 receptors and PG/COX system.

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“…Ghrelin was originally reported to exhibit gastroprotective activity against mucosal lesions induced by corrosive substances such as ethanol (Sibilia et al, 2003(Sibilia et al, , 2004 as well as against damage induced by stress (Brzozowski et al, 2004a;Konturek et al, 2004). In the present study, this peptide has been shown to attenuate the lesions caused by I/R, an effect accompanied by an increase in the GBF.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin/Cyclooxygenase Pathway in Ghrelin-Induced Gastroprotection against Ischemia-Reperfusion Injury

Brzozowski

Konturek²,

Śliwowski³

et al. 2006

J Pharmacol Exp Ther

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Ghrelin is involved in the control of food intake, but its role in gastroprotection against the formation of gastric mucosal injury has been little elucidated. We studied the effects of peripheral (i.p.) and central (i.c.v.) administration of ghrelin on gastric secretion and gastric mucosal lesions induced by 3 h of ischemia/reperfusion (I/R) with or without inhibition of ghrelin growth hormone secretagogue type 1a receptor (GHS-R1a) by using ghrelin antagonist, D-Lys 3 -GHRP-6; blockade of cycloox-and COX-2 (rofecoxib); and bilateral vagotomy or capsaicin denervation. I/R produced typical gastric erosions, a significant fall in the gastric blood flow (GBF), an increase in gastric myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) content, and the up-regulation of mucosal ghrelin mRNA. Ghrelin dose-dependently increased gastric acid secretion and significantly reduced I/R-induced gastric erosions, while producing a significant rise in the GBF and mucosal PGE 2 generation and a significant fall in MPO activity and MDA content. The protective and hyperemic activities of ghrelin were significantly attenuated in rats pretreated with D-Lys 3 -GHRP-6 and capsaicin denervation and completely abolished by vagotomy. Indomethacin, SC560, and rofecoxib, selective COX-1 and COX-2 inhibitors, attenuated ghrelin-induced protection that was restored by supplying the methyl analog of prostaglandin (PG) E 2 . The expression of mRNA for COX-1 was unaffected by ghrelin, but COX-2 mRNA and COX-2 protein were detectable in I/R injured mucosa and further up-regulated by exogenous ghrelin. We conclude that ghrelin exhibits gastroprotective and hyperemic activities against I/R-induced erosions, the effects that are mediated by hormone activation of GHS-R1a receptors, COX-PG system, and vagal-sensory nerves.

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Effects of hexarelin against acid-independent and acid-dependent ulcerogens in the rat

Cited by 15 publications

References 33 publications

Histamine H<sub>3</sub> Receptors Are Involved in the Protective Effect of Ghrelin against HCl-Induced Gastric Damage in Rats

Histamine H<sub>3</sub> Receptors Are Involved in the Protective Effect of Ghrelin against HCl-Induced Gastric Damage in Rats

Involvement of Orexigenic Peptides in the Mechanism of Gastric Mucosal Integrity and Healing of Chronic Gastric Ulcers

Prostaglandin/Cyclooxygenase Pathway in Ghrelin-Induced Gastroprotection against Ischemia-Reperfusion Injury

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