Nerve stimulation-induced nitric oxide release as a consequence of muscarinic M1 receptor activation
Autor: | C. Olgart, H. H. Iversen, Lars E. Gustafsson, N. Peter Wiklund |
---|---|
Rok vydání: | 1997 |
Předmět: |
Male
medicine.medical_specialty Colon Guinea Pigs Muscarinic Antagonists In Vitro Techniques Muscarinic Agonists Nitric Oxide chemistry.chemical_compound Internal medicine Muscarinic acetylcholine receptor M5 Muscarinic acetylcholine receptor medicine Muscarinic acetylcholine receptor M4 Animals Enzyme Inhibitors Pharmacology Chemistry Muscarinic acetylcholine receptor M3 Muscarinic acetylcholine receptor M2 Muscarinic acetylcholine receptor M1 Receptors Muscarinic Acetylcholine Electric Stimulation Endocrinology Telenzepine Luminescent Measurements Female Nitric Oxide Synthase medicine.drug Muscle Contraction |
Zdroj: | European journal of pharmacology. 331(2-3) |
ISSN: | 0014-2999 |
Popis: | The aim of the present study was to investigate whether nerve stimulation-induced nitric oxide (NO) release in the guinea-pig colon is affected by acetylcholine and to identify the muscarinic receptor subtype involved. Nerve-smooth muscle preparations were suspended in a superfusion chamber and NO/NO2- overflow in the superfusate was detected by chemiluminescence analysis. Transmural nerve stimulation evoked a significant increase in NO/NO2- release, which was inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME) and abolished by tetrodotoxin. Exogenous acetylcholine concentration-dependently increased NO/NO2- release and atropine reduced nerve stimulation-evoked NO/NO2- release. The muscarinic M1 receptor selective antagonist telenzepine (10(-8) M) was as effective as atropine (10(-6) M) in inhibiting NO/NO2- release. The muscarinic M3 receptor antagonists 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and para-fluoro-hexahydrosila-difenidol (p-F-HHSiD) markedly inhibited cholinergic contractions at 3 x 10(-8) M and 3 x 10(-7) M respectively, but did not affect NO/NO2- release. In conclusion, nerve-induced NO/NO2- release in the guinea-pig colon is to a substantial part due to muscarinic M1 receptor activation. Thus acetylcholine, a major contractile neurotransmitter in the gut, can release NO which could act as a negative feedback mechanism on intestinal smooth muscle or neuronal activity. |
Databáze: | OpenAIRE |
Externí odkaz: |