Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Heinemann, A; Holzer, P.
Intestinal motor depression by 7-nitroindazole through an action unrelated to nitric oxide synthase inhibition.
PHARMACOLOGY 1999 59: 310-320.
Doi: 10.1159/000028334
Web of Science
PubMed
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FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Heinemann Akos
- Holzer Peter
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- Abstract:
- Nitric oxide (NO) is a cotransmitter of inhibitory motor neurons of the enteric nervous system. This study examined the effect of 7-nitroindazole (7-NI), an inhibitor of neuronal NO synthase (NOS), on intestinal peristalsis and muscle activity and compared 7-NI with N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of NOS isoforms. Peristalsis in isolated segments of the guinea pig small intestine was triggered by a perfusion-induced rise of the intraluminal pressure. While L-NAME (10-300 micromol/l) lowered the peristaltic pressure threshold (PPT) at which propulsive muscle contractions were elicited, 7-NI (10-300 micromol/l) caused a concentration-related increase in PPT. L-Arginine (1-3 mmol/l) failed to reverse peristaltic motor depression evoked by 7-NI but annulled the L-NAME-evoked stimulation of peristalsis. Drugs which stimulated peristalsis, such as L-NAME, naloxone, apamin and suramin plus pyridoxal phosphate-6-azophenyl-2'-4'-disulphonic acid counteracted the inhibitory effect of submaximally effective concentrations of 7-NI on peristalsis. 7-NI (100-300 micromol/l) inhibited circular muscle contractions evoked by cholecystokinin octapeptide, the NK(1) receptor agonist GR-73,632 and indomethacin whereas L-NAME (100-300 micromol/l) failed to inhibit any drug-evoked contraction. These data show that 7-NI, unlike L-NAME, inhibits circular muscle contractions of the gut and depresses intestinal peristalsis. It is concluded that the inhibitory motor action of 7-NI is unrelated to inhibition of neuronal NOS and arises from depression of smooth muscle activity.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Dose-Response Relationship, Drug -
- Enzyme Inhibitors - pharmacology
- Female - pharmacology
- Gastrointestinal Motility - drug effects
- Guinea Pigs - drug effects
- Imidazoles - pharmacology
- In Vitro - pharmacology
- Indazoles - pharmacology
- Indomethacin - pharmacology
- Intestine, Small - drug effects
- Male - drug effects
- Muscle Contraction - drug effects
- Muscle, Smooth - drug effects
- NG-Nitroarginine Methyl Ester - pharmacology
- Nitric Oxide Synthase - antagonists and inhibitors
- Peptide Fragments - pharmacology
- Peristalsis - drug effects
- Research Support, Non-U.S. Gov't - drug effects
- Sincalide - pharmacology
- Substance P - analogs and derivatives
- Tetrodotoxin - pharmacology
- Find related publications in this database (Keywords)
- Nitric Oxide Synthase
- 7-Nitroindazole
- 1-(2-Trifluoromethylphenyl)Imidazole
- N-G-Nitro-L-Arginine Methyl Ester
- Intestinal Smooth Muscle
- Enteric Nervous System
- Intestinal Peristalsis