Nitric oxide regulation of migrating motor complex: randomized trial of N-G-monomethyl-L-arginine effects in relation to muscarinic and serotonergic receptor blockade

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Halim, M. AbdulUppsala universitet,Gastroenterologi/hepatologi (author)

Nitric oxide regulation of migrating motor complex : randomized trial of N-G-monomethyl-L-arginine effects in relation to muscarinic and serotonergic receptor blockade

Article/chapterEnglish2015

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2015-07-30
Wiley,2015
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LIBRIS-ID:oai:DiVA.org:uu-265826
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-265826URI
https://doi.org/10.1111/apha.12554DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:132127054URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Aim: The migrating motor complex (MMC) propels contents through the gastrointestinal tract during fasting. Nitric oxide (NO) is an inhibitory neurotransmitter in the gastrointestinal tract. Little is known about how NO regulates the MMC. In this study, the aim was to examine nitrergic inhibition of the MMC in man using N-G-monomethyl-L-arginine (L-NMMA) in combination with muscarinic receptor antagonist atropine and 5-HT3 receptor antagonist ondansetron. Methods: Twenty-six healthy volunteers underwent antroduodenojejunal manometry for 8 h with saline or NO synthase (NOS) inhibitor L-NMMA randomly injected I.V. at 4 h with or without atropine or ondansetron. Plasma ghrelin, motilin and somatostatin were measured by ELISA. Intestinal muscle strip contractions were investigated for NO-dependent mechanisms using L-NMMA and tetrodotoxin. NOS expression was localized by immunohistochemistry. Results: L-NMMA elicited premature duodenojejunal phase III in all subjects but one, irrespective of atropine or ondansetron. L-NMMA shortened MMC cycle length, suppressed phase I and shifted motility towards phase II. Pre-treatment with atropine extended phase II, while ondansetron had no effect. L-NMMA did not change circulating ghrelin, motilin or somatostatin. Intestinal contractions were stimulated by L-NMMA, insensitive to tetrodotoxin. NOS immunoreactivity was detected in the myenteric plexus but not in smooth muscle cells. Conclusion: Nitric oxide suppresses phase III of MMC independent of muscarinic and 5-HT3 receptors as shown by nitrergic blockade, and acts through a neurocrine disinhibition step resulting in stimulated phase III of MMC independent of cholinergic or 5-HT3-ergic mechanisms. Furthermore, phase II of MMC is governed by inhibitory nitrergic and excitatory cholinergic, but not 5-HT3-ergic mechanisms.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Gastroenterologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Gastroenterology and Hepatology hsv//eng
motility
myenteric plexus
N-G-monomethyl-L-arginine
nitric oxide
nitric oxide synthase

Added entries (persons, corporate bodies, meetings, titles ...)

Gillberg, LindaKarolinska Institutet,Uppsala universitet,Institutionen för medicinska vetenskaper (author)
Boghus, SandyUppsala universitet,Institutionen för medicinska vetenskaper (author)
Sundbom, MagnusUppsala universitet,Gastrointestinalkirurgi(Swepub:uu)magsundb (author)
Karlbom, UrbanUppsala universitet,Kolorektalkirurgi(Swepub:uu)urbakarl (author)
Webb, Dominic-LucUppsala universitet,Gastroenterologi/hepatologi(Swepub:uu)domwe127 (author)
Hellstrom, Per. M.Uppsala universitet,Gastroenterologi/hepatologi(Swepub:uu)perhe742 (author)
Uppsala universitetGastroenterologi/hepatologi (creator_code:org_t)

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In:Acta Physiologica: Wiley215:2, s. 105-1181748-17081748-1716

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By the author/editor: Halim, M. Abdul; Gillberg, Linda; Boghus, Sandy; Sundbom, Magnus; Karlbom, Urban; Webb, Dominic-Lu ...; show more...; Hellstrom, Per. ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Gastroenterology ...

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By the university: Uppsala University; Karolinska Institutet

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