Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157

Up to now, for gastric lesions potentiation or induction, as well as determ ination of endogenous dopamine significance, dopamine antagonist or dopamin e vesicle depletor were given separately. Therefore, without combination st udies, the evidence for dopamine significance remains split on either block ade of dopamine post-synaptic receptor or inhibition of dopamine storage, e ssentially contrasting with endogenous circumstances, where both functions could be simultaneously disturbed. For this purpose, a co-administration of reserpine and haloperidol, a dopamine granule depletor combined with a dop amine antagonist with pronounced ulcerogenic effect, was tested, and the ra ts were sacrificed 24 h after injurious agent(s) administration. Haloperido l (5 mg.kg(-1) b.w. i.p.), given alone, produced the lesions in all rats. R eserpine (5 mg.kg(-1) b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger t han in the groups injured with separate administration of either haloperido l or reserpine alone. Along with our previous results, when beneficial agen ts were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomoph ine 1 mg, amphetamine 20 mg.kg(-1) i.p.) apparently attenuated the otherwis e consistent haloperidol-gastric lesions. Likewise, an apparent inhibition of the reserpine-lesions was noted as well. However, if they were given in rats injured with combination of haloperidol and reserpine, their otherwise prominent beneficial effects were absent. Ranitidine (10 mg), omeprazole ( 10 mg), atropine (10 mg), pentadecapeptide BPC 157 (Gly-Glu-Pro-Pro-Pro-Gly -Lys-Pro-Ala-Asp-Ala-Gly-Leu-Val) (10 mu g or 10 ng.kg(-1) i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. C onfronted with potentiated lesions following a combination of haloperidol a nd reserpine, these agents maintained their beneficial effects, noted in th e rats treated with either haloperidol or reserpine alone. The failure of d opaminomimetics could be most likely due to more extensive inhibition of en dogenous dopamine system activity, and need for remained endogenous dopamin e for their salutary effect, whereas the beneficial activities of ranitidin e, omeprazole, atropine, pentadecapeptide BPC 157 following dopamine system inhibition by haloperidol+reserpine suggest their corresponding systems pa rallel those of dopamine system, and they may function despite extensive in hibition of endogenous dopamine system activity. (C) 2000 Elsevier Science Ltd. Published by Editions scientifiques et medicales Elsevier SAS.