Central ghrelin gastroprotection involves nitric oxide/prostaglandin cross‐talk

Abstract

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 mg per rat) injection on PGE 2 accumulation in normal or EtOH-lesioned gastric mucosa, (2) pretreatment with indomethacin (10 mg kg À1 , p.o.), a non-selective cyclooxygenase (COX) inhibitor, and with a selective COX-1, SC560 (5 mg kg À1 , p.o.) or COX-2 inhibitor, celecoxib (3.5 mg kg À1 , 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 À1 , 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.

Ghrelin and gastrointestinal wound healing. A new perspective for colorectal surgery

“…Intravenous ghrelin administration also induces inflammatory cytokines release, ameliorates intestinal barrier dysfunction and reduces neutrophil infiltration in I/Rinduced intestinal injury in animal models 62 . Intraperitoneal administration of ghrelin has increased gastric acid secretion and protected against water immersion and restraint stress injury in experimental study 63 . Adami et al 64 also have found protective effects in gastric lesions induced by intragastric administration of HCL in rats, this effect was abolished by prior administration of GHS-receptors antagonists and inhibition of histamine release.…”

The Role of Capsaicin-Sensitive Afferent Nerves in Gastric Mucosal Protection Initiated Centrally or Peripherally under Experimental Conditions

“…Hereafter, additional neuropeptides proved to be gastroprotective given centrally, among others adrenomedullin [128] peptide YY [129] amylin [130], leptin, cholecystokinin [131], ghrelin [132], opioids, e.g. β-endorphin, deltorphin II, endomorphins [4,133] nociceptin, nocistatin [134], TLQP-21, a VGF-derived peptide [135], substance P [136] and angiotensin II [137] (see reviews: [4,127,138]).…”

Nitric Oxide and Endothelin-1 in Children With Digestive Disorders

“…Эффекторные клетки системы подвергаются воз-действию ряда веществ гормональной природы, которые, тесно взаимодействуя между собой, объединяются в эндо-кринные регуляторные цепи [12,13]. В группе биологиче-ских соединений, принимающих активное участие в регу-ляции функций ЖКТ, важная роль в настоящее время отводится эндотелиальным факторам, что обусловлено их влиянием на большинство физиологических и патофизио-логических процессов пищеварительной системы [13][14][15].…”

“…Также было установлено, что молсидомин как донатор NO усиливал экспрессию супероксиддисмутазы, а также профилак-тировал ишемическое поражение тонкого кишечника у крыс [50]. Более того, цитопротективный эффект NO реализовывался не только через регуляцию кровотока в слизистой оболочке желудка, но и через опосредован-ное влияние на соматостатин, адреномедуллин, тирео-тропный гормон, гормон роста, грелин и холецистокинин [13,[51][52][53]. Описана протективная роль NO, которую связывали со стабилизацией функции тучных клеток: NO ингибировал выброс медиаторов воспаления, а также модулировал эффекты цитокинов, тем самым снижая сте-пень повреждения ЖКТ [15].…”