title: Central ghrelin gastroprotection involves nitric oxide/prostaglandin cross-talk.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milano, Milan, Italy. valeria.sibilia@unimi.it
authors.forename: V
authors.initials: V
authors.lastname: Sibilia
authors.forename: F
authors.initials: F
authors.lastname: Pagani
authors.forename: G
authors.initials: G
authors.lastname: Rindi
authors.forename: N
authors.initials: N
authors.lastname: Lattuada
authors.forename: D
authors.initials: D
authors.lastname: Rapetti
authors.forename: V
authors.initials: V
authors.lastname: De Luca
authors.forename: N
authors.initials: N
authors.lastname: Campanini
authors.forename: I
authors.initials: I
authors.lastname: Bulgarelli
authors.forename: V
authors.initials: V
authors.lastname: Locatelli
authors.forename: F
authors.initials: F
authors.lastname: Guidobono
authors.forename: C
authors.initials: C
authors.lastname: Netti
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D054439:Ghrelin; D012333:RNA, Messenger; D009569:Nitric Oxide; D000431:Ethanol; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone