Involvement of nitric oxide in the inhibitory innervation of the human isolated colon

Boeckxstaens, Guy E.; Pelckmans, Paul; Herman, Arnold G.; Maercke, Y. M. Van

doi:10.1016/0016-5085(93)91003-z

Cited by 136 publications

(74 citation statements)

References 30 publications

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“…We also suggested that PACAP mediates about half NANC relaxation in the distal colon of Wistar-ST rats via opening of apamin-sensitive K + channels [15,25]. A few reports also suggest association of ATP-mediated relaxation in the human colon [3] and ATP-mediated i.j.ps in the guinea pig colon [29] with apamin-sensitive K + channels. In all three strains studied, participation of PACAP in the relaxation was not shown in any regions other than the distal colon in the present study.…”

Section: Discussionmentioning

confidence: 71%

Mediators of Nonadrenergic, Noncholinergic Relaxation in Sprague Dawley Rat Intestine: Comparison with the Mediators of Other Strains.

Okishio¹,

Niioka²,

Yamaji³

et al. 2000

The Journal of Veterinary Medical Science

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ABSTRACT. Participation of nitric oxide, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) in nonadrenergic, noncholinergic (NANC) relaxation of longitudinal muscle of various intestinal regions in Sprague Dawley rats (8-weekold) was studied in vitro. Nitric oxide was suggested to participate in NANC relaxation of every intestinal region studied. But the participation was partial and its extent varied among the regions: significant in the proximal colon and rectum, and moderate in the jejunum, ileum and distal colon. Participation of PACAP in NANC relaxation was suggested only in the distal colon, while that of VIP was not detected in any of regions. Results obtained in the present study indicate that extent of participation of nitric oxide in NANC relaxation in Sprague Dawley rat intestine is more significant than those of other strains, Wistar and Wistar-ST.KEY WORDS: NANC (nonadrenergic noncholinergic) relaxation, nitric oxide, PACAP, rat intestine, VIP.J. Vet. Med. Sci. 62(8): 821-828, 2000 Nitric oxide has been suggested to mediate nonadrenergic, noncholinergic (NANC) relaxation in many regions of the gastrointestinal tract [22,23]. However, accumulated evidence suggests that the role of nitric oxide in NANC relaxation is not uniform throughout the gastrointestine, but quite variable in region to region. Wistar-ST rat intestine is a case in point. That is, an essential role of nitric oxide in the relaxation was suggested in circular [11] and longitudinal [24,26] muscles of the proximal colon, and in circular muscle of the rectum [27], while only minor or no role was suggested in longitudinal muscle of the jejunum [19] or the distal colon [16,24], respectively. In addition to regional difference, we recently found a strain difference in the mediator of NANC relaxation of the distal colon of rats between the Sprague Dawley and Wistar-ST strains: nitric oxide was suggested to partially mediate NANC relaxation of the Sprague Dawley but not Wistar-ST strain [21].In addition to nitric oxide, vasoactive intestinal peptide (VIP) is another candidate for the mediator of NANC relaxation in several gastrointestinal regions: lower oesophageal sphincter of opossums [5] and rabbits [2], stomach of dogs [1], guinea pigs [6, 10] and rats [13], taenia coli of guinea pigs [7,10], and colon of rats [9,24]. Pituitary adenylate cyclase activating peptide (PACAP) was also suggested to mediate NANC relaxation in some regions: lower oesophageal sphincter of cats and humans [20], stomach of guinea pigs [14], and colon of guinea pigs [12] and rats [8,15]. We suggested that VIP and PACAP mediate NANC relaxation of longitudinal muscle of the distal colon of Wistar-ST rats via opening of charybdotoxin-and apamin-sensitive K + channels, respectively [15,25]. However, participation of the peptides as well as nitric oxide in NANC relaxation does not seem to be uniform throughout the gastrointestine. For example, neither role of VIP in longitudinal muscle of the proximal and mid colon [24], a...

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Section: Discussionmentioning

confidence: 71%

Mediators of Nonadrenergic, Noncholinergic Relaxation in Sprague Dawley Rat Intestine: Comparison with the Mediators of Other Strains.

Okishio¹,

Niioka²,

Yamaji³

et al. 2000

The Journal of Veterinary Medical Science

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“…Morphological studies have shown that ATP and NO colocalize in neurons of the myenteric plexus of the rat colon (Belai & Burnstock, 1994), providing structural support to a pressumptive cotransmission. A mechanism of cotransmission between NO and another neurotransmitter, perhaps ATP, has been proposed in the circular muscle of human (Boeckxstaens et al, 1993) and guinea-pig (Zagorodnyuk & Maggi 1994;Selemedis et al, 1997) …”

Section: Discussionmentioning

confidence: 99%

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Plujà

Fernández

Jiménez

1999

British J Pharmacology

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1 The rat colonic circular muscle displays cyclic episodes of myenteric potential oscillations (MPOs), each of them associated with a spontaneous contraction. Nifedipine 1 mM abolished both MPOs and their associated contractions. TTX (1 mM) increased the amplitude and frequency of spontaneous contractions. 2 Electrical ®eld stimulation (EFS) induced a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (IJP), with two phases: an initial fast hyperpolarization (characterized by IJP amplitude) and a sustained hyperpolarization (characterized by IJP duration). 3 Sodium nitroprusside (10 mM) hyperpolarized and abolished spontaneous contractions even in presence of TTX or 1 mM apamin. ATP (100 mM) also hyperpolarized and abolished spontaneous contractions but its e ects were decreased by TTX and abolished by apamin. 4 Suramin (100 mM) or apamin reduced the amplitude of the IJPs, but did not a ect their duration. Incubation with L-NOARG (1 mM) reduced the duration but not the amplitude of the IJPs. In presence of L-NOARG plus suramin or L-NOARG plus apamin, both duration and amplitude of the IJPs were reduced but a residual IJP could still be recorded. 5 We conclude that the mechanical and electrical cyclic activity of the rat colonic circular muscle is modulated but not originated by the enteric nervous system and involves L-type calcium channel activity. EFS induces release of NANC inhibitory neurotransmitters which hyperpolarize and relax smooth muscle cells. Both ATP and NO are involved in IJP generation: ATP is responsible for the ®rst phase of the IJPs involving activation of apamin-sensitive potassium channels, whereas NO initiates the second phase which is independent of the activation of such channels.

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“…Such an effect would explain the reversal of the constipation due to morphine by L-arginine in the mouse (Calignano et al, 1991); a reduction in the force of contraction of ileal and colonic circular muscle in dogs has been reported (Stewart et al, 1975). NO also relaxes small intestinal and colonic circular smooth muscle (Boeckxstaens et al, 1993;Stark et al, 1993) and also seems to be involved in relaxation of the gut during the peristaltic reflex (Grider, 1993). In the latter case, vasoactive intestinal peptide (VIP) is postulated to interact with NO, whereby VIP stimulates the influx of calcium into muscle cells and activates constitutive NO synthase, liberating NO as the agonist of relaxation (Murthy et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…NO is an apparent mediator of the action of other laxatives (Mascolo et al, 1993;1994;Gaginella, personal communication). NO is an intestinal secretagogue (Tamai & Gaginella, 1994) and it relaxes intestinal smooth muscle (Boeckxstaens et al, 1993;Grider, 1993;Stark et al, 1993). This muscle relaxant effect is likely to enhance intestinal transit and contribute to a laxative/diarrhoeal effect (Gullikson & Bass, 1984).…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide as a mediator of the laxative action of magnesium sulphate

Izzo

Gaginella

Mascolo

et al. 1994

British J Pharmacology

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1Magnesium sulphate was studied for its effects on diarrhoea, fluid secretion, gastrointestinal transit and nitric oxide (NO) synthase activity in rats. 2 At a dose of 2 g kg-orally magnesium sulphate produced diarrhoea that was delayed in onset and intensity in a dose-related manner by the NO synthase inhibitor N0-nitro-L-arginine methyl ester (L-NAME). This was prevented by the NO precursor, L-arginine and the NO donating compound, isosorbide-5-mononitrate (IMN). 3 Nitric oxide synthase activity was stimulated in gut tissue from rats given magnesium sulphate and this was inhibited by L-NAME. Dexamethasone (1 mg kg-', i.p.), an inhibitor of inducible NO synthase, had no effect on magnesium sulphate-induced diarrhoea. 4 Magnesium sulphate stimulated fluid and electrolyte accumulation in the intestinal lumen; these effects were prevented by L-NAME but not D-NAME. 5 Gastrointestinal transit of a non-absorbable marker (charcoal suspension) was increased by oral magnesium sulphate from a mean value of 54.1% to 72.9% (P<0.01), and this was prevented by pretreatment with L-NAME. 6 The results demonstrate that oral magnesium sulphate produces diarrhoea in rats by increasing the accumulation of fluid in the intestinal lumen and enhancing flow from the proximal to distal intestine. The mechanism involves release of NO, probably through stimulation of the constitutive form of NO synthase. Whether or not the effects of magnesium sulphate are due to an osmotic action or an intrinsic effect of the magnesium or sulphate ions cannot be determined from these experiments.

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Involvement of nitric oxide in the inhibitory innervation of the human isolated colon

Cited by 136 publications

References 30 publications

Mediators of Nonadrenergic, Noncholinergic Relaxation in Sprague Dawley Rat Intestine: Comparison with the Mediators of Other Strains.

Mediators of Nonadrenergic, Noncholinergic Relaxation in Sprague Dawley Rat Intestine: Comparison with the Mediators of Other Strains.

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Nitric oxide as a mediator of the laxative action of magnesium sulphate

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