Non‐adrenergic non‐cholinergic inhibition of gastrointestinal smooth muscle and its intracellular mechanism(s)

Matsuda, Nilce Mitiko; Miller, Steven M.

doi:10.1111/j.1472-8206.2009.00761.x

Cited by 40 publications

(43 citation statements)

References 97 publications

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“…Although the involvement of each individual pathway has been suggested in several previous studies [29][30][31][32], this current study at the organ, cell and protein levels provides, to our knowledge, novel experimental evidence of the signaling pathways. The demonstration of the VIP effects in PA and its signaling pathways should have impact on the understanding of pulmonary circulation.…”

Section: Discussionmentioning

confidence: 80%

Vasoactive intestinal polypeptide relaxes isolated rat pulmonary artery rings through two distinct mechanisms

et al. 2010

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Vasoactive intestinal polypeptide (VIP), an endogenous neuropeptide normally present in lungs and other organs, relaxes pulmonary arteries (PAs) in different species, whereas the underlying mechanisms are still not fully understood. The aim of this study, therefore, is to investigate the signal transduction of VIP in the relaxation of isolated rat PA rings. The isometric tension of the rings was studied in vitro with force-electricity transducers. In endothelium-intact (EI) rings, VIP elicited concentration-dependent relaxation after the rings were pre-contracted by phenylephrine. A similar effect, though smaller, was observed in endothelium-denuded (ED) rings. Inhibition of the endothelial nitric oxide synthase (eNOS) by NG-nitro-L-arginine methyl ester diminished the VIP-induced vasodilatation of PA rings. The VIP-induced vasorelaxation was markedly reduced by the inhibition of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway with wortmannin and LY294002, respectively, which was seen in EI rings, but not in ED rings. Western blot analysis revealed that VIP increased the phosphorylation of eNOS at Ser 1177, but did not affect the overall expression of eNOS. In ED rings, the PKA inhibitor H-89 and K(ATP) channel inhibitor glibenclamide almost totally abolished the vasodilatation effect of VIP. The results suggested that the vasodilatation effect of VIP on rat PAs is mediated by both vascular endothelium and smooth muscle, involving respectively the PI3K/Akt-eNOS pathway and the PKA-K(ATP) channel pathway.

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Section: Discussionmentioning

confidence: 80%

Vasoactive intestinal polypeptide relaxes isolated rat pulmonary artery rings through two distinct mechanisms

et al. 2010

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“…As both of these transmitter substances produce excitatory responses in intestinal smooth muscle (Hoyle and Burnstock, 1989;Furness, 2000), the enhanced release of adenosine may attenuate the activity of smooth muscle. Adenosine itself has inhibitory actions on smooth muscle, through the enhanced production of cyclic AMP (Giron et al, 2008;Matsuda and Miller, 2010). Thus, most of the factors involved in the generation of excitatory responses in intestinal smooth muscle cells may be attenuated by the enhanced release of adenosine.…”

Section: Discussionmentioning

confidence: 99%

Carbon dioxide-induced inhibition of mechanical activity in gastrointestinal smooth muscle preparations isolated from the guinea-pig

Fujimoto

Shigemasa

Suzuki

2011

J. Smooth Muscle Res.

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Mechanical responses of smooth muscle elicited by application of CO2-gas bubbled physiological salt solution (CO2-gas solution) were investigated in isolated stomach antrum and colon preparations of the guinea-pig. Circular smooth muscle preparations of both colon and stomach were spontaneously active with periodic generation of phasic contractions. In colonic preparations, the CO2-gas solution produced a biphasic response, with an initial small transient contraction followed by a sustained inhibition of phasic contractions. Removal of the CO2-gas solution allowed a slow recovery of the spontaneous contractions over a period of about 40 min. The recovery developed with a similar time course irrespective of the length of time exposed to CO2-gas solution. The inhibitory responses elicited by CO2-gas solution were not modulated by atropine, N  -nitro-L-arginine or neostigmine. Atropine-sensitive excitatory responses of smooth muscle elicited by transmural nerve stimulation or exogenously applied acetylcholine were attenuated or abolished in the presence of CO2-gas solution. In stomach preparations, the CO2-gas solution elicited a tri-phasic response, with an initial transient relaxation followed by a transient contraction and then a sustained inhibition of the rhythmic contractions. The peak amplitude of the transient contraction was about 2.5 times larger than the spontaneous phasic contractions. The pH of the CO2-gas solution was reduced to about 6. Application of pH 6 solution again produced a tri-phasic response, as was the case for the CO2-gas solution, however the amplitude of the transient contraction was only about 0.4 times that of the spontaneous contractions. The re-appearance of the abolished phasic contraction was quicker with the pH 6 solution (about 1.8 min) than it was for the CO2-gas solution (about 6 min). The inhibitory responses elicited by the CO2-gas solution could be simulated only partly by the acidified solution, and a possible involvement of additional factors in the inhibition elicited by CO2-gas solution was considered.

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“…Following this equilibration period, the strips were exposed to EFS with trains of 100 pulses of 0.5 ms, 30 V, and 10 Hz for 10 s to evoke smooth muscle contraction and relaxation. When the NANC responses were recorded, atropine (1 μmol/l) and guanethidine (5 μmol/l) were used to block the cholinergic responses and exclude the adrenergic responses, respectively [21,22]. Preparations of L-NNA, SnPP-IX, MRS2179, α-chymotrypsin, ODQ, ryanodine, thapsigargin, apamin, ChTX, and iberiotoxin were directly added to the bath at least 10 min prior to each experiment for testing.…”

Section: Methodsmentioning

confidence: 99%

Evidence that Nitric Oxide Is a Non-Adrenergic Non-Cholinergic Inhibitory Neurotransmitter in the Circular Muscle of the Mouse Distal Colon: A Study on the Mechanism of Nitric Oxide-Induced Relaxation

et al. 2014

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The gastrointestinal tract is composed of outer longitudinal muscle layers and inner circular muscle layers. Nitric oxide (NO), carbon monoxide (CO), and ATP play major roles as non-adrenergic non-cholinergic (NANC) inhibitory neurotransmitters in the longitudinal muscle of the mouse distal colon, whereas it is unclear which NANC inhibitory neurotransmitters are in its circular muscle. We investigated the electric field stimulation (EFS)-induced relaxations in the circular smooth muscle of the distal colon under NANC conditions. In the experiments in which N^ω-nitro-L-arginine, an inhibitor of NO synthase, was added, the EFS-induced relaxation decreased in a concentration-dependent manner and finally vanished. In contrast, CO, purinergic receptor ligands, and peptidergic substances do not play major roles as NANC neurotransmitters in the circular muscle of the mouse distal colon. ODQ, an inhibitor of soluble guanylate cyclase, strongly attenuated EFS-induced relaxation. Ryanodine, a Ca²⁺ release modulator at the sarcoplasmic reticulum, strongly attenuated EFS-induced relaxation as well. Relaxation induced by NOR-1, which generates NO, was inhibited by ODQ and ryanodine. Next, we performed experiments that simultaneously measured tension and the cytoplasmic Ca²⁺ concentration ([Ca²⁺]_cyt). NOR-1 decreased the tension and [Ca²⁺]_cyt levels in the circular muscle. ODQ and ryanodine strongly attenuated the NOR-1-induced change in both tension and [Ca²⁺]_cyt levels. In this study, we demonstrate that NO functions as a NANC inhibitory neurotransmitter in the circular muscle obtained from the mouse distal colon.

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Non‐adrenergic non‐cholinergic inhibition of gastrointestinal smooth muscle and its intracellular mechanism(s)

Cited by 40 publications

References 97 publications

Vasoactive intestinal polypeptide relaxes isolated rat pulmonary artery rings through two distinct mechanisms

Vasoactive intestinal polypeptide relaxes isolated rat pulmonary artery rings through two distinct mechanisms

Carbon dioxide-induced inhibition of mechanical activity in gastrointestinal smooth muscle preparations isolated from the guinea-pig

Evidence that Nitric Oxide Is a Non-Adrenergic Non-Cholinergic Inhibitory Neurotransmitter in the Circular Muscle of the Mouse Distal Colon: A Study on the Mechanism of Nitric Oxide-Induced Relaxation

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