Purinergic nerves mediate the non-nitrergic relaxation of the human ileum in response to electrical field stimulation

Undi, Sarolta; Benkó, Rita; Wolf, Matyas; Illényi, L; Horváth, Örs Péter; Antal, A; Csontos, Zsolt; Vereczkei, András; Barthó, L.

doi:10.1016/j.brainresbull.2006.09.008

Cited by 7 publications

(10 citation statements)

References 18 publications

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“…However, several results are inconsistent with the hypothesis that NO is the sole NANC inhibitory neurotransmitter in the human GI tract: 1) the fast component of the IJP is L-NNA insensitive (15, 21). 2) in the presence of NO synthase inhibitors, an important NANC-nonnitrergic relaxation is present (6,29,31). These results are consistent with the presence of at least one complementary inhibitory neurotransmitter, which might have complementary or redundant functions.…”

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confidence: 67%

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Purinergic and nitrergic junction potential in the human colon

Gallego

Gil²,

Aleu³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

120

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The aim of the present work is to investigate a putative junction transmission [nitric oxide (NO) and ATP] in the human colon and to characterize the electrophysiological and mechanical responses that might explain different functions from both neurotransmitters. Muscle bath and microelectrode techniques were performed on human colonic circular muscle strips. The NO donor sodium nitroprusside (10 M), but not the P2Y receptor agonist adenosine 5Ј-O-2-thiodiphosphate (10 M), was able to cause a sustained relaxation. N G -nitro-L-arginine (L-NNA) (1 mM), a NO synthase inhibitor, but not 2Ј-deoxy-N 6 -methyl adenosine 3Ј,5Ј-diphosphate tetraammonium salt (MRS 2179) (10 M), a P2Y antagonist, increased spontaneous motility. Electrical field stimulation (EFS) at 1 Hz caused fast inhibitory junction potentials (fIJPs) and a relaxation sensitive to MRS 2179 (10 M). EFS at higher frequencies (5 Hz) showed biphasic IJP with fast hyperpolarization sensitive to MRS 2179 followed by sustained hyperpolarization sensitive to L-NNA; both drugs were needed to fully block the EFS relaxation at 2 and 5 Hz. Two consecutive single pulses induced MRS 2179-sensitive fIJPs that showed a rundown. The rundown mechanism was not dependent on the degree of hyperpolarization and was present after incubation with L-NNA (1 mM), hexamethonium (100 M), MRS 2179 (1 M), and NF023 (10 M). We concluded that single pulses elicit ATP release from enteric motor neurons that cause a fIJP and a transient relaxation that is difficult to maintain over time; also, NO is released at higher frequencies causing a sustained hyperpolarization and relaxation. These differences might be responsible for complementary mechanisms of relaxation being phasic (ATP) and tonic (NO).ATP; IJP; smooth muscle; rundown; purinergic receptors THE IDENTITY OF THE INHIBITORY neurotransmitter(s) involved in nonadrenergic, noncholinergic (NANC) inhibitory neurotransmission is still being debated, but ATP and nitric oxide (NO) are presently recognized as two of the major inhibitory mediators in the gastrointestinal (GI) tract. Nitrergic neurons mediate lower esophageal sphincter relaxation after swallowing (34), and vagally induced gastric (11) and pyloric (2) relaxation regulate colonic transit time (26) and mediate the rectoanal inhibitory reflex (28). Fewer studies have been published on the putative role of ATP as a neurotransmitter mediating these physiological functions. ATP and NO might participate in the regulation of gastroduodenal motility in rats, (17) and ATP might participate in vagally induced gastric relaxation (4) and intrinsic gastric adaptive relaxation in mice (12). These (and other) data suggest that these neurotransmitters have important physiological functions; however, smooth muscle relaxation might have different properties (i.e., tonic vs. phasic) that should be better characterized. The release of inhibitory neurotransmitter(s) at the neuromuscular junction is the final step for smooth muscle relaxation. Inhibitory junction potentials (IJPs) have been well c...

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confidence: 67%

“…(5,31). However, 2Ј-deoxy-N 6 -methyl adenosine 3Ј,5Ј-diphosphate tetraammonium salt (MRS 2179), which is the N 6 -methyl modification of 2Ј-deoxyadenosine 3Ј,5Ј-bisphosphate, is a potent P2Y 1 receptor antagonist (8) and is presently considered competitive and specific (1,19).…”

mentioning

confidence: 99%

Purinergic and nitrergic junction potential in the human colon

Gallego

Gil²,

Aleu³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

120

View full text Add to dashboard Cite

show abstract

“…A purinergic mediation of the non-nitrergic component of the non-adrenergic, non-cholinergic (NANC) relaxation of the circular muscle (CM) of human ileum in response to electrical field stimulation has been reported by Undi et al (2006). The neurotransmitter background of the NANC inhibition in the longitudinal muscle (LM) has not been elucidated.…”

Section: Introductionmentioning

confidence: 98%

“…A combination of the P 2 purinoceptor antagonists PPADS (50 μM) and suramin (100 μM) was used in the experiments of Undi et al (2006) and Benko et al (2007) for studying a participation of purinergic mechanisms in the NANC relaxation of the CM of the human ileum and sigmoid colon, respectively. This combination of antagonists was more effective than either substance alone.…”

Section: Introductionmentioning

confidence: 99%

The NANC relaxation of the human ileal longitudinal and circular muscles is inhibited by MRS 2179, a P2 purinoceptor antagonist

et al. 2009

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“…ATP released by stimulation of enteric nerves mediates the non-nitrergic relaxation of the human ileum (Undi et al 2006). X-ray examination of gastric motility in healthy volunteers showed that ATP-evoked rapid relaxation of the intestine and stomach (Kasakov and Vlaskovska 2003).…”

Section: Stomachmentioning

confidence: 98%