ABSTRACT
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 micromol L(-1)) significantly increased the optical density of NADPH-d positive neurones, while blockade of nitric oxide synthase with N(omega)-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 micromol 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.
Subject(s)
Muscle, Smooth/physiology , Nitrergic Neurons/physiology , Receptors, Muscarinic/physiology , Stomach/innervation , Synaptic Transmission/physiology , Animals , Electric Stimulation , Enzyme Inhibitors/pharmacology , Guinea Pigs , Immunohistochemistry , Male , Muscarinic Agonists/pharmacology , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle Relaxation/drug effects , Muscle Relaxation/physiology , Muscle, Smooth/drug effects , NADPH Dehydrogenase/metabolism , Nitrergic Neurons/drug effects , Nitric Oxide/metabolism , Nitric Oxide Synthase/drug effects , Nitric Oxide Synthase/metabolism , Organ Culture Techniques , Receptors, Muscarinic/drug effects , Stomach/drug effects , Synaptic Transmission/drug effectsABSTRACT
The effect of activation of muscarinic acetylcholine subtype M1 receptors on the electrical field stimulation (EFS)-induced contractions in cat duodenal muscle strips was investigated. EFS elicited two types of responses: a) on-contraction; and b) off-contraction. The EFS-evoked responses were tetrodotoxin- and atropine-sensitive. In all strips the muscarinic acetylcholine subtype M1 agonist (4-Hydroxy-2-butynyl)-1-trimethylammonium-m-chlorocarbanilate chloride (McN-A-343) increased the tone and the amplitude of the spontaneous contractions. On this background EFS produced an inhibition of the phasic contractions at switching on the stimulation, followed by off-contractions. The EFS-induced inhibition was removed by N omega-nitro-L-arginine and was partly overcome by L-arginine. The results suggest the participation of muscarinic acetylcholine subtipe M1 receptors in the mediation of nitrergic inhibitory responses in cat duodenum.
