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 mug per rat) injection on PGE(2) 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 PGE(2) 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 PGE(2) in normal mucosa, whereas, it reversed the EtOH-induced PGE(2) 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 PGE(2) surge induced by ghrelin and, like indomethacin, reduced EtOH-induced PGE(2) 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 PGE(2) are involved in ghrelin gastroprotective activity.
Central ghrelin gastroprotection involves nitric oxide/prostaglandin cross-talk / V. Sibilia, F. Pagani, G. Rindi, N. Lattuada, D. Rapetti, V. De Luca, N. Campanini, I. Bulgarelli, V. Locatelli, F. Guidobono, C. Netti. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - 154:3(2008 Jun), pp. 688-697.
|Titolo:||Central ghrelin gastroprotection involves nitric oxide/prostaglandin cross-talk|
SIBILIA, VALERIA (Primo)
PAGANI, FRANCESCA (Secondo)
GUIDOBONO CAVALCHINI, FRANCESCA (Penultimo)
NETTI, CARMELA (Ultimo)
|Parole Chiave:||Celecoxib; Cyclooxygenase; Ethanol; Gastric ulcers; Ghrelin; Indomethacin; Nitric oxide; Prostaglandins; SC560|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||giu-2008|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/bjp.2008.120|
|Appare nelle tipologie:||01 - Articolo su periodico|