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Regul Pept ; 181: 50-66, 2013 Feb 10.
Article in English | MEDLINE | ID: mdl-23327997

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.


Subject(s)
Anti-Ulcer Agents/pharmacology , Arrhythmias, Cardiac/drug therapy , Hyperkalemia/drug therapy , Nitric Oxide/metabolism , Peptide Fragments/pharmacology , Proteins/pharmacology , Action Potentials/drug effects , Administration, Oral , Animals , Arginine/pharmacology , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/mortality , Blood Pressure/drug effects , Electrolytes/blood , Gastric Mucosa/metabolism , HEK293 Cells , Heart/drug effects , Heart Rate/drug effects , Humans , Hyperkalemia/chemically induced , Hyperkalemia/metabolism , Hyperkalemia/mortality , Injections, Intraperitoneal , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/antagonists & inhibitors , Patch-Clamp Techniques , Potassium Chloride/poisoning , Rats , Rats, Wistar , Stomach/drug effects , Stomach/pathology , Survival Analysis
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