| Role of phospholipase A2 (group I secreted) in the genesis of basal tone in the internal anal sphincter smooth muscle. | |
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MedLine Citation:
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PMID: 17717042 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of phospholipase A(2) (PLA(2)) in the genesis of basal tone in the internal anal sphincter (IAS) is not known. We determined the effects of PLA(2) and inhibitors on the basal tone and intraluminal pressures (IASP) in the rat IAS vs. rectal smooth muscles (RSM). In addition, we determined the correlations between the IAS tone, PLA(2) levels, and the actual enzymatic activity. Inhibition of PLA(2) by 4-bromophenacyl bromide (universal inhibitor of PLA(2)) and MJ33 [selective inhibitor of secreted isoform of PLA(2) (sPLA(2))] caused concentration-dependent decrease in the IAS tone and in the IASP. Maximal decreases in the IAS tone and IASP by 4-bromophenacyl bromide and MJ33 were 58.8 +/- 6.9 and 51.5 +/- 6.3%, and 66.7 +/- 5.1 and 79.8 +/- 8.2%, respectively. The sPLA(2) inhibitors were approximately 100 times more potent in decreasing the IASP than the mean blood pressure. Conversely, the selective inhibitors of the cytosolic and calcium-independent PLA(2) arachidonyl trifluoromethyl ketone and bromoenol lactone, respectively, produced no significant effect. The IAS had characteristically higher levels of sPLA(2) activity (26.5 +/- 4.9 micromol.min(-1).ml(-1)) vs. the RSM (3.2 +/- 0.4 micromol.min(-1).ml(-1)), and higher levels of sPLA(2) as shown by Western blot and RT-PCR. Interestingly, administration of sPLA(2) transformed RSM into the tonic smooth muscle like that of the IAS: it developed basal tone and relaxed in response to the electrical field stimulation. From the present data, we conclude that sPLA(2) plays a critical role in the genesis of tone in the IAS. PLA(2) inhibitors may provide potential therapeutic target for treating anorectal motility disorders. |
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Authors:
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Márcio A F de Godoy; Satish Rattan |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-08-23 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 293 ISSN: 0193-1857 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2007 Nov |
Date Detail:
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Created Date: 2007-11-06 Completed Date: 2007-12-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G979-86 Citation Subset: IM |
Affiliation:
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Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA 19107, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acids / pharmacology Enzyme Inhibitors / pharmacology Male Muscle Tonus / physiology* Muscle, Smooth / physiology* Phospholipases A2 / antagonists & inhibitors, genetics, physiology* RNA, Messenger / genetics Rats Rats, Sprague-Dawley Rectum / physiology |
| Grant Support | |
ID/Acronym/Agency:
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DK35385/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/Enzyme Inhibitors; 0/RNA, Messenger; 149301-79-1/arachidonyltrifluoromethane; EC 3.1.1.4/Phospholipases A2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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