In:
Pharmacology, S. Karger AG, Vol. 89, No. 5-6 ( 2012), p. 287-294
Abstract:
〈 b 〉 〈 i 〉 Aim: 〈 /i 〉 〈 /b 〉 In the present study we examined whether histamine H 〈 sub 〉 4 〈 /sub 〉 receptors (H 〈 sub 〉 4 〈 /sub 〉 Rs) have a role in gastric ulcerogenesis using a mouse model of gastric damage. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The H 〈 sub 〉 4 〈 /sub 〉 R antagonist JNJ7777120 and the H 〈 sub 〉 4 〈 /sub 〉 R agonists VUF8430 and VUF10460 were investigated in fasted CD-1 mice against the ulcerogenic effect induced by co-administration of indomethacin (IND, 30 mg/kg s.c.) and bethanechol (BET, 5 mg/kg i.p.). Both macroscopic and histologic lesions were examined. Strain-related differences were investigated by testing JNJ7777120 also in NMRI, BALB/c and C57BL/6J mice. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Neither JNJ7777120 nor the H 〈 sub 〉 4 〈 /sub 〉 R agonists displayed effects in the normal stomach at any dose tested (10 and 30 mg/kg s.c.). As expected, IND+BET provoked several lesions in the fundic mucosa, which were significantly reduced by JNJ7777120 (10 and 30 mg/kg s.c.). The gastroprotective effect of JNJ7777120 (10 and 30 mg/kg s.c.) was observed in CD-1, NMRI and BALB/c, but not in C57BL/6J, mice. In CD-1 mice, the H 〈 sub 〉 4 〈 /sub 〉 R agonists VUF8430 and VUF10460 (both at 10 and 30 mg/kg s.c.) did not modify the damage induced by IND+BET, however VUF8430 (10 mg/kg s.c.) prevented the gastroprotection induced by JNJ7777120 (10 mg/kg s.c.). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Data obtained with selective ligands suggest that the H 〈 sub 〉 4 〈 /sub 〉 R may have a role in mouse gastric ulcerogenesis. If confirmed in humans, these data would emphasize the potential advantage of H 〈 sub 〉 4 〈 /sub 〉 R blockers as gastrosparing anti-inflammatory drugs. The lack of effects of JNJ7777120 in C57BL/6J mice has to be carefully considered in the pharmacological characterization of H 〈 sub 〉 4 〈 /sub 〉 R functions and/or new selective ligands.
Type of Medium:
Online Resource
ISSN:
0031-7012
,
1423-0313
Language:
English
Publisher:
S. Karger AG
Publication Date:
2012
detail.hit.zdb_id:
1483550-2
SSG:
15,3
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