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Sökning: id:"swepub:oai:DiVA.org:liu-88365" > The type 2 CCK/gast...

  • Webb, Dominic-LucUppsala universitet,Gastroenterologi/hepatologi,Uppsala University, Sweden (författare)

The type 2 CCK/gastrin receptor antagonist YF476 acutely prevents NSAID-induced gastric ulceration while increasing iNOS expression

  • Artikel/kapitelEngelska2013

Förlag, utgivningsår, omfång ...

  • 2012-11-24
  • Springer Verlag (Germany),2013
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-88365
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-88365URI
  • https://doi.org/10.1007/s00210-012-0812-5DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:rkh:diva-1430URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:125916053URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:du-23700URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-193524URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|GlaxoSmithKline||Karolinska Institutet||Uppsala University||Bengt Ihres Foundation||Socialstyrelsen||
  • YF476 differs from the proton pump inhibitor (PPI) esomeprazole in mode of action by antagonizing the type 2 receptor of cholecystokinin/gastrin (CCK-2R). YF476 protection against diclofenac-induced gastric ulcers was compared to esomeprazole and correlated with plasma levels of hormones related to gastric pH (gastrin, ghrelin, and somatostatin), gastric gene expression of these hormones, their receptors, and inducible nitric oxide synthase (iNOS). YF476 or esomeprazole pretreatments were followed by diclofenac. Four hours later, gastric tissue was excised and analyzed for ulcer index. An intragastrically implanted Bravo capsule measured pH for 5 days during YF476 plus pentagastrin treatment. Changes in gene expression were assayed for gastrin, ghrelin, and somatostatin; their receptors; and iNOS. YF476 acutely (within 4 h) protected against diclofenac-induced gastric ulcers equivalent to esomeprazole. Gastric pH recorded during 5 days in the presence of pentagastrin was 1.83 (+/- 0.06). YF476 raised pH to 3.67 (+/- 0.09) and plasma ghrelin, gastrin, and somatostatin increased. YF476 increased gene expression of somatostatin receptor and gastrin, while ghrelin receptor decreased; transcripts coding ghrelin, somatostatin, and CCK-2R remained unchanged. In the presence of diclofenac, esomeprazole increased expression of all these transcripts and that of iNOS, while YF476 yielded only decreased CCK-2R and increased iNOS transcripts. YF476 is a potential new preventative treatment for patients at risk of nonsteroidal antiinflammatory drug (NSAID)-induced ulceration. Gastric gene expressions of ghrelin, gastrin, and somatostatin and their receptors differ between esomeprazole and YF476. Despite these differences and different modes of action to raise gastric pH, both drugs acutely increase iNOS, suggesting iNOS expression parallels pH.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Rudholm-Feldreich, TobiasUppsala universitet,Gastroenterologi/hepatologi,Uppsala University, Sweden(Swepub:du)trf (författare)
  • Gillberg, LindaKarolinska Institutet,Karolinska University Hospital, Sweden (författare)
  • Halim, AbdulUppsala universitet,Gastroenterologi/hepatologi,Uppsala University, Sweden(Swepub:uu)abdab535 (författare)
  • Theodorsson, ElvarÖstergötlands Läns Landsting,Linköpings universitet,Klinisk kemi,Hälsouniversitetet,Clinical Chemistry, Linköping University(Swepub:liu)elvth65 (författare)
  • Sanger, Gareth J.University of London, England,lizard Institute, Neurogastroenterology group, Queen Mary, University of London, Harlow, UK (författare)
  • Campbell, Colin A.GlaxoSmithKline, England,Neurology & GI CEDD, GlaxoSmithKline, Harlow, UK (författare)
  • Boyce, MalcolmHammersmith Medical Research, England,Hammersmith Medicines Research, London, UK (författare)
  • Naslund, ErikKarolinska Institutet,Danderyd Hospital, Sweden (författare)
  • Hellström, Per M.Uppsala universitet,Gastroenterologi/hepatologi,Uppsala University, Sweden(Swepub:uu)perhe742 (författare)
  • Uppsala universitetGastroenterologi/hepatologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Naunyn-Schmiedeberg's Archives of Pharmacology: Springer Verlag (Germany)386:1, s. 41-490028-12981432-1912

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