Autor: |
Kortezova, N. I., Shikova, L. I., Milusheva, E. A., Itzev, D. E., Bagaev, V. A., Mizhorkova, Z. N. |
Předmět: |
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Zdroj: |
Neurogastroenterology & Motility; Apr2004, Vol. 16 Issue 2, p155-165, 11p, 1 Diagram, 5 Graphs |
Abstrakt: |
Muscarinic receptor activation by (4-Hydroxy-2-butynyl)-1-trimethylammonium-m-chlorocarbanilate chloride (McN-A-343) was investigated both on NADPH-d staining and on electrically induced responses in guinea-pig gastric fundus. McN-A-343 (10 μmol L−1) significantly increased the optical density of NADPH-d positive neurones, while blockade of nitric oxide synthase with N ω-nitro-L-arginine (L-NA) decreased it, suggesting facilitation of nitric oxide (NO) production. Electrical field stimulation (EFS; 2 Hz, 0.2 ms, supramaximal current intensity, 10 s train duration) elicited on-contraction followed by off-relaxation in the circular muscle strips. McN-A-343 (10 μmol L−1) transformed the EFS-evoked response from on-contraction into on-relaxation, which was neurogenic, tetrodotoxin-sensitive and hexamethonium-resistant. L-NA partly reduced the EFS-evoked relaxation, revealing two components: a nitrergic and a non-nitrergic one. The effect of McN-A-343 on the amplitude of the EFS-evoked relaxation was not changed by the M3 receptor antagonist para-fluoro-hexahydro-sila-difenidol hydrochloride, but was significantly enhanced by M1 receptor blockade with telenzepine. In the presence of telenzepine, the L-NA-dependent nitrergic component of the EFS-induced relaxation predominates. We suggest that cholinergic receptor activation has a dual effect on nitrergic neurotransmission: (i) stimulation of NOS by muscarinic receptor(s) different from M1 and M3 subtype, (ii) prejunctional inhibition of NO-mediated relaxation via M1 receptors. In addition, M1 receptors may facilitate the non-nitrergic relaxation. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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