Abstract | 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. |
Abstract (english) | 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. |