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Muscarinic modulation of nitrergic neurotransmission in guinea‐pig gastric fundus
Author(s) -
Kortezova N. I.,
Shikova L. I.,
Milusheva E. A.,
Itzev D. E.,
Bagaev V. A.,
Mizhorkova Z. N.
Publication year - 2004
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2004.00514.x
Subject(s) - endocrinology , muscarinic acetylcholine receptor , medicine , chemistry , neurotransmission , tetrodotoxin , stimulation , nitric oxide synthase , acetylcholine , nitric oxide , hexamethonium , muscarinic acetylcholine receptor m1 , receptor
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 μ mol 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 μ mol 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 M 3 receptor antagonist para ‐fluoro‐hexahydro‐sila‐difenidol hydrochloride, but was significantly enhanced by M 1 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 M 1 and M 3 subtype, (ii) prejunctional inhibition of NO‐mediated relaxation via M 1 receptors. In addition, M 1 receptors may facilitate the non‐nitrergic relaxation.