title: Mortal hyperkalemia disturbances in rats are NO-system related. The life saving effect of pentadecapeptide BPC 157.
abstract: We demonstrate the full counteracting ability of stable gastric pentadecapeptide BPC 157 against KCl-overdose (intraperitoneal (i), intragastric (ii), in vitro (iii)), NO-system related. (i) We demonstrated potential (/kg) of: BPC 157 (10ng, 10μg ip, complete counteraction), l-arginine (100mg ip, attenuation) vs. L-NAME (5mg ip, deadly aggravation), given alone and/or combined, before or after intraperitoneal KCl-solution application (9mEq/kg). Therapy was confronted with promptly unrelenting hyperkalemia (>12mmol/L), arrhythmias (and muscular weakness, hypertension, low pressure in lower esophageal and pyloric sphincter) with an ultimate and a regularly inevitable lethal outcome within 30min. Previously, we established BPC 157-NO-system interaction; now, a huge life-saving potential. Given 30min before KCl, all BPC 157 regimens regained sinus rhythm, had less prolongation of QRS, and had no asystolic pause. BPC 157 therapy, given 10min after KCl-application, starts the rescue within 5-10min, completely restoring normal sinus rhythm at 1h. Likewise, other hyperkalemia-disturbances (muscular weakness, hypertension, low sphincteric pressure) were also counteracted. Accordingly with NO-system relation, deadly aggravation by L-NAME: l-arginine brings the values to the control levels while BPC 157 always completely nullified lesions, markedly below those of controls. Combined with l-arginine, BPC 157 exhibited no additive effect. (ii) Intragastric KCl-solution application (27mEq/kg) - (hyperkalemia 7mmol/L): severe stomach mucosal lesions, sphincter failure and peaked T waves were fully counteracted by intragastric BPC 157 (10ng, 10μg) application, given 30min before or 10min after KCl. (iii). In HEK293 cells, hyperkalemic conditions (18.6mM potassium concentrations), BPC 157 directly affects potassium conductance, counteracting the effect on membrane potential and depolarizations caused by hyperkalemic conditions.
authors: Department of Pharmacology, University of Zagreb, Medical School, Salata 11, 10000 Zagreb, Croatia.
authors: Ivan
authors: I
authors: Barisic
authors: Diana
authors: D
authors: Balenovic
authors: Robert
authors: R
authors: Klicek
authors: Bozo
authors: B
authors: Radic
authors: Bojana
authors: B
authors: Nikitovic
authors: Domagoj
authors: D
authors: Drmic
authors: Mario
authors: M
authors: Udovicic
authors: Dean
authors: D
authors: Strinic
authors: Darija
authors: D
authors: Bardak
authors: Lidija
authors: L
authors: Berkopic
authors: Viktor
authors: V
authors: Djuzel
authors: Marko
authors: M
authors: Sever
authors: Ivan
authors: I
authors: Cvjetko
authors: Zeljko
authors: Z
authors: Romic
authors: Aleksandra
authors: A
authors: Sindic
authors: Martina Lovric
authors: ML
authors: Bencic
authors: Sven
authors: S
authors: Seiwerth
authors: Predrag
authors: P
authors: Sikiric
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D001794:Blood Pressure / Q000187:drug effects; D004573:Electrolytes / Q000097:blood; D005753:Gastric Mucosa / Q000378:metabolism; D057809:HEK293 Cells; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D007274:Injections, Intraperitoneal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011189:Potassium Chloride / Q000506:poisoning; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000897:Anti-Ulcer Agents; D004573:Electrolytes; D010446:Peptide Fragments; D011506:Proteins; D009569:Nitric Oxide; D011189:Potassium Chloride; C083833:BPC 157; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester