Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 154, Issue 3, Pages 688-697Publisher
WILEY
DOI: 10.1038/bjp.2008.120
Keywords
ghrelin; ethanol; gastric ulcers; prostaglandins; cyclooxygenase; nitric oxide; indomethacin; celecoxib; SC560
Categories
Ask authors/readers for more resources
Background and purpose: Ghrelin, a gut-brain peptide, is considered a gastroprotective factor in gastric mucosa. We investigated the role of prostaglandins (PG) and the possible interplay between PGs and nitric oxide (NO) in ghrelin gastroprotection against ethanol (EtOH)-induced gastric lesions. Experimental approach: We examined the effects of (1) central ghrelin (4 mu g per rat) injection on PGE2 accumulation in normal or EtOH-lesioned gastric mucosa, (2) pretreatment with indomethacin (10 mg kg(-1), p.o.), a non-selective cyclooxygenase (COX) inhibitor, and with a selective COX-1, SC560 (5 mg kg(-1), p.o.) or COX- 2 inhibitor, celecoxib (3.5 mg kg(-1), p.o.) on ghrelin gastroprotection against 50% EtOH (1 mL per rat)-induced gastric lesions, (3) the NO synthase inhibitor, L-NAME (70 mg kg(-1), s.c), on gastric PGE2 content in ghrelin-treated rats and (4) central ghrelin on the expression of constitutive and inducible NOS and COX mRNA and on the localization of the immunoreactivity for COX- 2 in the gastric mucosa exposed to EtOH. Key results: Ghrelin increased PGE2 in normal mucosa, whereas, it reversed the EtOH-induced PGE2 surge. Ghrelin had no effect on mucosal COX- 1 expression but reduced the EtOH-induced increase in COX-2 expression and immunoreactivity. Indomethacin and SC560, but not celecoxib, removed ghrelin gastroprotection. L-NAME prevented the PGE2 surge induced by ghrelin and, like indomethacin, reduced EtOH-induced PGE2 increase. Ghrelin enhanced eNOS expression and reduced iNOS mRNA. Conclusions and implications: This study shows that COX-1-derived PGs are mainly involved in ghrelin gastroprotection and that the constitutive-derived NO together with PGE2 are involved in ghrelin gastroprotective activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available