| Sepiapterin reverses the changes in gastric nNOS dimerization and function in diabetic gastroparesis. | |
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MedLine Citation:
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PMID: 20731778 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: We have demonstrated previously that in vivo supplementation of tetrahydrobiopterin (BH₄); a co-factor for neuronal nitric oxide synthase (nNOS) significantly restored delayed gastric emptying and attenuated nitrergic relaxation in diabetic rat. In this study, we have investigated whether supplementation of sepiapterin (SEP), a precursor for BH₄ biosynthesis via salvage pathway restores gastric emptying and nitrergic system in female diabetic rats. METHODS: Diabetic rats (streptozotocin-induced) were supplemented with BH₄ or SEP (20 mg kg⁻¹ body weight). Gastric nitrergic relaxation in the presence or absence of high glucose and SEP were measured by electric field stimulation. Gastric muscular strips from healthy or diabetic female rats were incubated in the presence or absence of high glucose, SEP and/or methotrexate (MTX). Nitric oxide release was measured colorimetrically by NO assay kit. The expression of nNOSα and dimerization was detected by Western blot. KEY RESULTS: In vitro studies on gastric muscular tissues showed that MTX, an inhibitor of BH₄ synthesis via salvage pathway, significantly decreased NO release. In vivo treatment with MTX reduced both gastric nitrergic relaxation and nNOSα dimerization. Supplementation of SEP significantly attenuated delayed gastric emptying in diabetic rats. In addition, SEP supplementation restored impaired nitrergic relaxation, gastric nNOSα protein expression, and dimerization in diabetic rats. CONCLUSIONS & INFERENCES: The above data suggests that supplementation of SEP accelerated gastric emptying and attenuated reduced gastric nNOSα expression, and dimerization. Therefore, SEP supplementation is a potential therapeutic option for female patients of diabetic gastroparesis. |
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Authors:
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P R R Gangula; S Mukhopadhyay; P J Pasricha; K Ravella |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-08-22 |
Journal Detail:
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Title: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Volume: 22 ISSN: 1365-2982 ISO Abbreviation: Neurogastroenterol. Motil. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-08 Completed Date: 2011-02-28 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 9432572 Medline TA: Neurogastroenterol Motil Country: England |
Other Details:
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Languages: eng Pagination: 1325-31, e351-2 Citation Subset: IM |
Copyright Information:
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© 2010 Blackwell Publishing Ltd. |
Affiliation:
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Department of Physiology, Center for Women's Health Research, Meharry Medical College, Nashville, TN 37208, USA. pgangula@mmc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism Body Weight Diabetic Neuropathies / drug therapy*, physiopathology* Dietary Supplements Dimerization Female Gastric Emptying / drug effects Gastroparesis / drug therapy* Immunosuppressive Agents / administration & dosage, pharmacology, therapeutic use Male Methotrexate / administration & dosage, pharmacology, therapeutic use Nitric Oxide Synthase Type I / metabolism* Protein Structure, Quaternary Pterins / administration & dosage, pharmacology, therapeutic use* Rats Rats, Sprague-Dawley Stomach / drug effects, physiopathology* |
| Grant Support | |
ID/Acronym/Agency:
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3R1DKO76704-03S1//PHS HHS; G12 RR003032-26/RR/NCRR NIH HHS; G12 RR003032-26S1/RR/NCRR NIH HHS; G12 RR003032-27/RR/NCRR NIH HHS; G12RR03032/RR/NCRR NIH HHS; R21 DK076704-01A2/DK/NIDDK NIH HHS; R21 DK076704-02/DK/NIDDK NIH HHS; R21 DK076704-03/DK/NIDDK NIH HHS; R21 DK076704-03S1/DK/NIDDK NIH HHS; R21DKO76704//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Immunosuppressive Agents; 0/Pterins; 17094-01-8/sepiapterin; 59-05-2/Methotrexate; EC 1.14.13.39/Nitric Oxide Synthase Type I |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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