Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Dembinska-Kiec, A; Pallapies, D; Simmet, T; Peskar, BM; Peskar, BA.
Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection.
Br J Pharmacol. 1991; 104(4): 811-816.
Doi: 10.1111/j.1476-5381.1991.tb12511.x
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- Führende Autor*innen der Med Uni Graz
- Peskar Bernhard
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- Abstract:
- 1. The interactions between carbenoxolone and nitric oxide (NO) were examined by investigating their effects on human platelet aggregation, on rat aortic strips precontracted by phenylephrine and on protection of rat gastric mucosa against ethanol-induced injury. 2. Carbenoxolone (100-300 microM) caused a significant and concentration-dependent potentiation of rat peritoneal neutrophil (RPN)- 3-morpholino-syndnonimine (SIN-1)- or iloprost-induced inhibition of platelet aggregation. Higher concentrations (500 microM) of carbenoxolone alone markedly inhibited platelet aggregation. Pretreatment with carbenoxolone (100-300 microM) antagonized the reversal of the RPN- or SIN-1-induced antiaggregatory effect by oxyhaemoglobin (10 microM). 3. Rat aortic strips with intact endothelium precontracted by phenylephrine (0.1-0.3 microM) were relaxed by carbenoxolone (100-300 microM) in a concentration-dependent manner. Relaxations were abolished by mechanical removal of the endothelium or by incubation with methylene blue (10 microM) or NG-nitro-L-arginine (L-NNA, 100 microM). Sodium nitroprusside (10 nM)-induced relaxations of endothelium-denuded rat aortic strips were potentiated by carbenoxolone (100 microM). . The carbenoxolone (200 mg kg-1, p.o.)-induced gastroprotection against ethanol was antagonized by L-NNA (5-40 mg kg-1) in a dose-dependent manner. Pretreatment of rats with indomethacin (10 mg kg-1, s.c.) increased the effect of L-NNA. 5. The results suggest that the activity of carbenoxolone in the experimental systems tested is due to phosphodiesterase inhibition, although radical scavenging properties of the drug could contribute to some of the effects observed. In the rat gastric mucosa both increased prostaglandin levels and effects on the NO system could contribute to the protective action of carbenoxolone.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Aorta - drug effects
- Arginine - analogs and derivatives
- Carbenoxolone - antagonists and inhibitors
- Gastric Mucosa - drug effects
- Humans - drug effects
- Iloprost - pharmacology
- Male - pharmacology
- Methylene Blue - pharmacology
- Molsidomine - analogs and derivatives
- Muscle Relaxation - drug effects
- Muscle Tonus - drug effects
- Neutrophils - drug effects
- Nitric Oxide - metabolism
- Nitroarginine - metabolism
- Nitroprusside - pharmacology
- Oxyhemoglobins - pharmacology
- Rats - pharmacology
- Rats, Inbred Strains - pharmacology
- Stomach Ulcer - chemically induced
- Vasodilator Agents - pharmacology
- Find related publications in this database (Keywords)
- CARBENOXOLONE
- NITRIC OXIDE
- GASTROPROTECTION
- PLATELET AGGREGATION
- RAT AORTIC STRIPS
- PLATELET LEUKOCYTE INTERACTION
- NG-NITRO-L-ARGININE (L-NNA)
- 3-MORPHOLINO-SYDNONIMINE (SIN-1)