Nitric oxide (NO) increases acetylcholine release from and inhibits smooth muscle contraction of guinea-pig gastric fundus

Sotirov, E.; Papasova, M; Sántha, Ernö

doi:10.1016/s0361-9230(99)00019-2

Cited by 10 publications

(4 citation statements)

References 44 publications

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“…Functionally, SNP was also unable to augment the vagal bradycardia or increase the evoked release of acetylcholine in the presence of guanylyl cyclase inhibition, suggesting that release of NO and stimulation of guanylyl cyclase is responsible for the effects of SNP (rather than nitrosylation or generation of superoxide radicals caused by some NO donors; Sarkar et al 2000). Similarly, others have shown that NO increases the release of acetylcholine in rat forebrain (Prast & Philippu, 1992) and isolated synaptosomes (Morot Gaudry‐Talarmain et al 1997), and that NOS inhibition decreases the release of acetylcholine in guinea‐pig gastric fundus (Sotirov et al 1999).…”

Section: Discussionmentioning

confidence: 89%

Nitric oxide‐cGMP pathway facilitates acetylcholine release and bradycardia during vagal nerve stimulation in the guinea‐pig in vitro

Herring

Paterson

2001

The Journal of Physiology

119

104

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We tested the hypothesis that nitric oxide (NO) augments vagal neurotransmission and bradycardia via phosphorylation of presynaptic calcium channels to increase vesicular release of acetylcholine. The effects of enzyme inhibitors and calcium channel blockers on the actions of the NO donor sodium nitroprusside (SNP) were evaluated in isolated guinea‐pig atrial‐right vagal nerve preparations. SNP (10 μm) augmented the heart rate response to vagal nerve stimulation but not to the acetylcholine analogue carbamylcholine (100 nm). SNP also increased the release of [3H]acetylcholine in response to field stimulation. No effect of SNP was observed on either the release of [3H] acetylcholine or the HR response to vagal nerve stimulation in the presence of the guanylyl cyclase inhibitor 1H‐(1,2,4)‐oxadiazolo‐(4,3‐a)‐quinoxalin‐1‐one (ODQ, 10 μm). The phosphodiesterase 3 (PDE 3) inhibitor milrinone (1 μm) increased the release of [3H] acetylcholine and the vagal bradycardia and prevented any further increase by SNP. SNP was still able to augment the vagal bradycardia in the presence of the protein kinase G inhibitor KT5823 (1 μm) but not after protein kinase A (PKA) inhibition with H‐89 (0.5 μm) or KT5720 (1 μm) had reduced the HR response to vagal nerve stimulation. Neither milrinone nor H‐89 changed the HR response to carbamylcholine. SNP had no effect on the magnitude of the vagal bradycardia after inhibition of N‐type calcium channels with ω‐conotoxin GVIA (100 nm). These results suggests that NO acts presynaptically to facilitate vagal neurotransmission via a cGMP‐PDE 3‐dependent pathway leading to an increase in cAMP‐PKA‐dependent phosphorylation of presynaptic N‐type calcium channels. This pathway may augment the HR response to vagal nerve stimulation by increasing presynaptic calcium influx and vesicular release of acetylcholine.

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Section: Discussionmentioning

confidence: 89%

Nitric oxide‐cGMP pathway facilitates acetylcholine release and bradycardia during vagal nerve stimulation in the guinea‐pig in vitro

Herring

Paterson

2001

The Journal of Physiology

119

104

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“…The neurally dependent response of the guinea‐pig stomach fundus comprises of an acetylcholine‐dependent contractile component (blockable by atropine), and a relaxatory one which is believed to depend on the release of NO (at stimulation frequencies below 10 Hz) and vasoactive intestinal polypeptide (at stimulation frequencies above 10 Hz). Thus, at stimulation frequencies between 1 and 5 Hz, NO is practically the only relaxatory neurotransmitter to be released by EFS in this tissue (Sotirov et al . 1999, Sotirov & Papasova 2000).…”

Section: Contraction Studiesmentioning

confidence: 99%

Induction of heme oxygenase in guinea‐pig stomach: roles in contraction and in single muscle cell ionic currents

Kadinov¹,

Itzev²,

Gagov³

et al. 2002

Acta Physiologica Scandinavica

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The role of heme oxygenase reaction products in modulation of stomach fundus excitability was studied. The presence of constitutive heme oxygenase 2 was verified in myenteric ganglia by immunohistochemistry. The role of inducible heme oxygenase isoenzyme was investigated after invivo treatment of animals with CoCl2 (80 mg kg-1 b.w) injected subcutaneously 24 h before they were killed. This treatment resulted in increased production of bilirubin and positive staining for the inducible isoform in stomach smooth muscle and vast induction in the liver. In both control and treated animals haemin, applied to the bath as a substrate of heme oxygenase caused significant decrease of prostaglandin F2alpha-induced tone, and ameliorated the relaxatory response of the fundic strips to electrical field stimulation. Both effects were antagonized by Sn-protoporphyrin IX, competitive heme oxygenase inhibitor, and were found to be neuronally dependent. In single freshly isolated smooth muscle cells from control animals haemin caused a concentration-dependent increase of the whole cell K+ currents, which was not affected by Sn-protoporphyrin IX, cyclic guanosine monophosphate (cGMP)-dependent protein kinase or guanylyl cyclase antagonists, but was reversed by various antioxidants and abolished by an NO scavenger. In cells from treated animals the K+ current increasing effect of haemin did not depend on the presence of antioxidants, but was abolished by protein kinase G and guanylyl cyclase inhibitors, depletors of intracellular Ca2+ pools or Sn-protoporphyrin IX. Biliverdin did not affect contraction or ionic currents. Thus, this is the first study demonstrating that heme oxygenase is an inducible enzyme in guinea-pigs, which exerts a modulatory role on gastric smooth muscle excitability via carbon monoxide production.

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“…The effects of the NOS inhibitor L ‐NNA (Sigma, Zwijndrecht, The Netherlands) and the NO donor Sp‐NO (Calbiochem, Breda, The Netherlands) on neurotransmission failure were determined during hypoxia and hyperoxia. A final concentration of 1 mM L ‐NNA was used 18, 36, 43. It has been shown that 0.3 mM L ‐NNA increases cholinergic transmission in strips of canine colonic circular muscle,36 and that both 1 mM and 10 mM L ‐NNA increase submaximal tetanic force of the rat diaphragm in vitro during hyperoxia, which was more pronounced at high concentration 7, 18.…”

Section: Methodsmentioning

confidence: 99%

Nitric oxide modulates neuromuscular transmission during hypoxia in rat diaphragm

Zhu¹,

Heunks²,

Ennen³

et al. 2005

Muscle and Nerve

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Hypoxia impairs neuromuscular transmission in the rat diaphragm. In previous studies, we have shown that nitric oxide (NO) plays a role in force modulation of the diaphragm under hypoxic conditions. The role of NO, a neurotransmitter, on neurotransmission in skeletal muscle under hypoxic conditions is unknown. The effects of the NO synthase (NOS) inhibitor nomega-nitro-L-arginine (L-NNA, 1 mM) and the NO donor spermine NONOate (Sp-NO, 1 mM) were evaluated on neurotransmission failure during nonfatiguing and fatiguing contractions of the rat diaphragm under hypoxic (PO 2 ϳ 5.8 kPa) and hyperoxic conditions (PO 2 ϳ 64.0 kPa). Hypoxia impaired force generated by both muscle stimulation at 40 HZ (P 40 M) and by nerve stimulation at 40 HZ (P 40 N). The effect of hypoxia in the latter was more pronounced. L-NNA increased P 40 N whereas Sp-NO decreased P 40 N during hypoxia. In contrast, neither L-NNA nor Sp-NO affected P 40 N during hyperoxia. L-NNA only slightly reduced neurotransmission failure during fatiguing contractions under hyperoxic conditions. Consequently, neurotransmission failure assessed by comparing force loss during repetitive nerve simulation and superimposed direct muscle stimulation was more pronounced in hypoxia, which was alleviated by L-NNA and aggravated by Sp-NO. These data provide insight in the underlying mechanisms of hypoxia-induced neurotransmission failure. This is important as respiratory muscle failure may result from hypoxia in vivo. Respiratory muscle fatigue, especially that of the diaphragm, is a possible contributor to the development of respiratory failure-for instance, in patients with chronic obstructive pulmonary disease (COPD). 24 Diaphragm fatigue may be the result of a failure of the muscle tissue itself to generate force (contractile fatigue) or failure in neuromuscular transmission. 3 In vitro studies indicate that the contribution of neurotransmission failure to muscle fatigue ranges from 18% 17 to as much as 75%. 1 The importance of neuromuscular transmission failure in the development of respiratory failure has also been demonstrated in intact animals. 5 Hypoxia, a common feature in several respiratory diseases including COPD, adult respiratory distress syndrome, and pneumonia, impairs neuromuscular transmission in the rat diaphragm. 4 However, little is known about the underlying mechanisms of hypoxiainduced neurotransmission failure in the respiratory muscles. In skeletal muscle, nitric oxide (NO) plays a role in the regulation of neural transmission. 31,47 Skeletal muscle is a major source for NO in the body 32 and neuronal NO synthase (nNOS) is present in high concentrations at the postsynaptic surface of the neuromuscular junction of both fast-and slowtwitch fibers. 7,21 Furthermore, NO appears to influence acetylcholine release from presynaptic terminals in several types of neuromuscular junction models, including skeletal muscle. 31,37 We have previously shown that hypoxia-induced impairment in rat diaphragm contractile performance is associated with el...

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Nitric oxide (NO) increases acetylcholine release from and inhibits smooth muscle contraction of guinea-pig gastric fundus

Cited by 10 publications

References 44 publications

Nitric oxide‐cGMP pathway facilitates acetylcholine release and bradycardia during vagal nerve stimulation in the guinea‐pig in vitro

Nitric oxide‐cGMP pathway facilitates acetylcholine release and bradycardia during vagal nerve stimulation in the guinea‐pig in vitro

Induction of heme oxygenase in guinea‐pig stomach: roles in contraction and in single muscle cell ionic currents

Nitric oxide modulates neuromuscular transmission during hypoxia in rat diaphragm

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