Neuroleptici, donji jednjačni i pilorički sfinkter, sustav dušik oksida i pentadekapeptid BPC 157

Belošić Halle, Željka (2015) Neuroleptici, donji jednjačni i pilorički sfinkter, sustav dušik oksida i pentadekapeptid BPC 157. PhD thesis, Sveučilište u Zagrebu.

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Abstract

It is not known how dopamine antagonists, L-NAME, L-arginine and stable gastric pentadecapeptide BPC-157 would interact with lower esophageal and pyloric sphincter pressure in rats (LES, PS). We revealed a fall in pressure within LES and PS as an indicative class effect of peripherally and centrally acting antipsihotics. In addition, given intraperitoneally alone and/or combined, all agents once daily through seven days, last application 24h before pressure assessment, BPC-157 mostly dose-dependently, counteracts all pressure falls induced by all antipsihotics; L-NAME induced a marked fall in both sphincters and worsened haloperidol and domperidone-failure; Larginine induced a smaller fall in both sphincters, but reversed L-NAME effect, and partly counteracted dopamine antagonists failure effect (haloperidol (LES)) as well as worsening of both haloperidol (LES) and domperidone (PS)- failure induced by L-NAME. Additional counteracting effect of BPC-157 was general, including all pressure decrease otherwise induced by L-NAME or Larginine, as well as complete counteraction of both spihnicters pressure worsening of haloperidol and domperidone (PS)-failure otherwise induced by L-NAME administration. In conclusion, counteracting potential of BPC-157 (as well as counteracting potential of L-arginine) can be against the conditions of dopamine receptor blockade and NOS-blockade.

Abstract in Croatian

Nije poznato kako antagonisti dopamina, L-NAME, L-arginin i želučani pentadekapeptid BPC-157 utječu na donji ezofagusni (DES) i pilorusni sfinkter (PS) u štakora. Otkrili smo pad tlaka DES-a i PS-a koji je posljedica učinka antipsihotika kao skupine u cjelini, te antiemetika, što uključuje sve testirane antagoniste dopamina i centralne (haloperidol, kvetiapin, olanzapin, flufenazin, klorpromazin, klozapin, levomepromazin, metoklopramid, sulpirid) i periferne (domperidon). Osim toga, BPC-157 primjenjen intraperitonealno sam i/ili u kombinaciji, jednom dnevno tijekom sedam dana u većoj dozi (10μg/kg), neutralizira pad tlaka izazvan antipsihoticima. L-NAME je izazvao značajan pad oba sfinktera i dodatno pogoršao haloperidolom i domperidonom izazvan pad tlaka, a L-arginin je doveo do manjeg pada tlaka oba sfinktera, ali je antagonizirao učinak L-NAME. L-arginin je djelomično neutralizirao učinak dopaminskih antagonista (haloperidol-DES), te pad tlaka izazvan haloperidolom (DES) i domperidonom (PS) koji su još više pogoršani dodavanjem L-NAME. Dodatni antagonizirajući učinak BPC-157 je neutralizacija pada tlaka sfinktera koji je induciran primjenom L-NAME ili Larginina, kao što je i kompletno poništenje pada tlaka izazvanog primjenom haloperidola i domperidona (PS), dodatno potenciranog primjenom L-NAME. U zaključku, antagonizirajući potencijal BPC-157 (i antagonizirajući potencijal L-arginina) bi mogao doći do izražaja u stanjima kao što su blokada dopaminskih receptora i blokada sustava dušičnog oksida.

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