The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure.
The known effects of a novel stomach pentadecapeptide BPC157 (10 microg or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.)-induced gastric lesions (simultaneously applied i.p.) and in blood pressure maintenance (given i.v.), were investigated in rats challenged with a combination of N(G)-nitro-L-arginine methylester (L-NAME) (5 mg/kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-generation and NO precursor, L-arginine (200 mg/kg i.v.) (D-arginine was ineffective). In the gastric lesions assay, NO agents were given 5 min before ethanol injury and BPC 157 medication. Given alone, BPC157 had an antiulcer effect, as did L-arginine, but L-NAME had no effect. L-NAME completely abolished the effect of L-arginine, whereas it only attenuated the effect of BPC 157. After application of the combination of L-NAME + L-arginine, the BPC157 effect was additionally impaired. In blood pressure studies, compared with L-arginine, pentadecapeptide BPC 157 (without effect on basal normal values) had both a mimicking effect (impaired L-NAME-blood pressure increase, when applied prophylactically and decreased already raised L-NAME values, given at the time of the maximal L-NAME-blood pressure increase (i.e., 10 min after L-NAME)) and preventive activity (L-arginine-induced moderate blood pressure decrease was prevented by BPC 157 pretreatment). When BPC 157 was given 10 min after L-NAME + L-arginine combination, which still led to a blood pressure increase, its previously clear effect (noted in L-NAME treated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 microM) as L-arginine, induced a comparable generation of NO. But, BPC 157 effect could not be inhibited by L-NAME, even when L-NAME was given in a tenfold (100 versus 1000 microM) higher dose than that needed for inhibition of the L-arginine effect. NO synthesis was blunted when the pentadecapeptide BPC 157 and L-arginine were combined. In summary, BPC 157 could interfere with the effects of NO on both gastric mucosal integrity and blood pressure maintenance in a specific way, especially with L-arginine, having a more prominent and/or particularly different effect from that of NO.
Sikirić
P
P
Center for Digestive Diseases, Medical Faculty, University of Zagreb, Croatia.
Seiwerth
S
S
Grabarević
Z
Z
Rucman
R
R
Petek
M
M
Jagić
V
V
Turković
B
B
Rotkvić
I
I
Mise
S
S
Zoricić
I
I
Konjevoda
P
P
Perović
D
D
Jurina
L
L
Separović
J
J
Hanzevacki
M
M
Artuković
B
B
Bratulić
M
M
Tisljar
M
M
Gjurasin
M
M
Miklić
P
P
Stancić-Rokotov
D
D
Slobodnjak
Z
Z
Jelovac
N
N
Marović
A
A
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011506:Proteins; D009569:Nitric Oxide; D000431:Ethanol; C083833:BPC 157; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester