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 determination of endogenous dopamine significance, dopamine antagonist or dopamine vesicle depletor were given separately. Therefore, without combination studies, the evidence for dopamine significance remains split on either blockade of dopamine post-synaptic receptor or inhibition of dopamine storage, essentially 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 dopamine antagonist with pronounced ulcerogenic effect, was tested, and the rats were sacrificed 24 h after injurious agent(s) administration. Haloperidol (5 mg x kg(-1) b.w. i.p.), given alone, produced the lesions in all rats. Reserpine (5 mg x kg(-1) b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger than in the groups injured with separate administration of either haloperidol or reserpine alone. Along with our previous results, when beneficial agents were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomophine 1 mg, amphetamine 20 mg x kg(-1) i.p.) apparently attenuated the otherwise 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-Asp-Ala-Gly-Leu-Val) (10 microg or 10 ng x kg(-1) i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. Confronted with potentiated lesions following a combination of haloperidol and reserpine, these agents maintained their beneficial effects, noted in the rats treated with either haloperidol or reserpine alone. The failure of dopaminomimetics could be most likely due to more extensive inhibition of endogenous dopamine system activity, and need for remained endogenous dopamine for their salutary effect, whereas the beneficial activities of ranitidine, omeprazole, atropine, pentadecapeptide BPC 157 following dopamine system inhibition by haloperidol+reserpine suggest their corresponding systems parallel those of dopamine system, and they may function despite extensive inhibition of endogenous dopamine system activity.
Sikiric
P
P
Department of Pharmacology, Medical Faculty University of Zagreb, Croatia.
Separovic
J
J
Buljat
G
G
Anic
T
T
Stancic-Rokotov
D
D
Mikus
D
D
Duplancic
B
B
Marovic
A
A
Zoricic
I
I
Prkacin
I
I
Lovric-Bencic
M
M
Aralica
G
G
Ziger
T
T
Perovic
D
D
Jelovac
N
N
Dodig
G
G
Rotkvic
I
I
Mise
S
S
Seiwerth
S
S
Turkovic
B
B
Grabarevic
Z
Z
Petek
M
M
Rucman
R
R
D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001285:Atropine / Q000627:therapeutic use*; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D005753:Gastric Mucosa / Q000473:pathology*; D006220:Haloperidol; D008297:Male; D009853:Omeprazole / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011506:Proteins / Q000627:therapeutic use*; D011899:Ranitidine / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000897:Anti-Ulcer Agents; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D010446:Peptide Fragments; D011506:Proteins; D001285:Atropine; D011899:Ranitidine; D012110:Reserpine; C083833:BPC 157; D006220:Haloperidol; D009853:Omeprazole; D004298:Dopamine