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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2000-2-4
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pubmed:abstractText |
Adrenomedullin (AM), a hypotensive peptide isolated from human pheochromocytoma, inhibits the proliferation of mesangial cells (MC) induced by mitogens such as platelet-derived growth factor. Quite recently, we have demonstrated that transmural pressure applied to cultured MC increased DNA synthesis and cell proliferation through protein kinase C and tyrosine kinase pathways. However, the modulatory effect of AM on pressure-induced cell proliferation is as yet unknown. In the present study, we examined the effect of AM on transmural pressure-induced DNA synthesis in cultured rat MC. Pressure was applied to cells placed in a sealed chamber using compressed helium. Application of pressure resulted in an increase in [(3)H]thymidine incorporation (approximately 2.0-fold). AM clearly inhibited pressure-induced DNA synthesis in a concentration-dependent manner. This inhibition was paralleled by an increase in cellular cAMP levels evoked by AM. Forskolin and dibutyryl cAMP mimicked the inhibitory effect of AM. The protein kinase A inhibitor H-89 significantly attenuated the effect of AM. Human AM(22-52)-NH(2), a putative AM receptor antagonist, reversed the inhibitory effects of AM more potently than did human CGRP(8-37), a calcitonin gene related peptide receptor antagonist. Our results suggest that AM, by acting mainly on AM-sensitive receptors, inhibits pressure-induced DNA synthesis in cultured rat MC through activation of protein kinase A. AM may play a protective role against MC proliferation in certain pathological conditions.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenomedullin,
http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitonin Gene-Related Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-(4-bromocinnamylamino)ethyl)-5-...,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenomedullin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/adrenomedullin (22-52),
http://linkedlifedata.com/resource/pubmed/chemical/calcitonin gene-related peptide...
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pubmed:status |
MEDLINE
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pubmed:issn |
0028-2766
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 1999 S. Karger AG, Basel
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pubmed:issnType |
Print
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pubmed:volume |
83
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
352-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10575297-Adrenomedullin,
pubmed-meshheading:10575297-Animals,
pubmed-meshheading:10575297-Bucladesine,
pubmed-meshheading:10575297-Calcitonin Gene-Related Peptide,
pubmed-meshheading:10575297-Cell Division,
pubmed-meshheading:10575297-Cells, Cultured,
pubmed-meshheading:10575297-Cyclic AMP,
pubmed-meshheading:10575297-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:10575297-DNA,
pubmed-meshheading:10575297-Enzyme Activation,
pubmed-meshheading:10575297-Enzyme Inhibitors,
pubmed-meshheading:10575297-Forskolin,
pubmed-meshheading:10575297-Glomerular Mesangium,
pubmed-meshheading:10575297-Humans,
pubmed-meshheading:10575297-Isoquinolines,
pubmed-meshheading:10575297-Membrane Proteins,
pubmed-meshheading:10575297-Peptide Fragments,
pubmed-meshheading:10575297-Peptides,
pubmed-meshheading:10575297-Pressure,
pubmed-meshheading:10575297-Rats,
pubmed-meshheading:10575297-Receptors, Adrenomedullin,
pubmed-meshheading:10575297-Receptors, Peptide,
pubmed-meshheading:10575297-Sulfonamides
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pubmed:year |
1999
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pubmed:articleTitle |
Adrenomedullin inhibits transmural pressure induced mesangial cell proliferation through activation of protein kinase A.
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pubmed:affiliation |
2nd Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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