Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-5-22
pubmed:abstractText
Adrenomedullin (AM), a potent vasorelaxant and natriuretic peptide isolated from human pheochromocytoma, is present in the kidney and secreted from endothelial cells (EC) and vascular smooth muscle cells (VSMC), but the functional role of AM is still unclear. To clarify the significance of AM as a local regulator, we investigated its secretion and action in cultured cells, and examined the effects of neutralization using a specific monoclonal antibody against AM. The prepared antibody directed against the ring structure showed a high affinity for human and rat AM. Using radioimmunoassay with this antibody, we found significant secretion from cultured rat mesangial cells (MC) of a 6-kDa mature form of AM as seen from EC and VSMC. The addition of AM into cultured cells dose-dependently increased cAMP production and potently inhibited PDGF-stimulated thymidine incorporation. Pretreatment with the monoclonal antibody completely abolished cAMP increase induced by exogenous AM. Moreover, antibody neutralization of endogenously secreted AM in cultured EC, but not in MC or VSMC, markedly (by approximately 70%) reduced basal cAMP production and significantly (1.7-fold) enhanced DNA synthesis. These results indicate that AM, acting as an autocrine/paracrine regulator, exerts an antiproliferative action on EC and MC, and suggest its role as a local modulator of endothelial and mesangial function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
979-85
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9551407-Adrenomedullin, pubmed-meshheading:9551407-Animals, pubmed-meshheading:9551407-Antibodies, Monoclonal, pubmed-meshheading:9551407-Aorta, pubmed-meshheading:9551407-Autocrine Communication, pubmed-meshheading:9551407-Cattle, pubmed-meshheading:9551407-Cell Division, pubmed-meshheading:9551407-Cells, Cultured, pubmed-meshheading:9551407-Cyclic AMP, pubmed-meshheading:9551407-Endothelium, pubmed-meshheading:9551407-Glomerular Mesangium, pubmed-meshheading:9551407-Humans, pubmed-meshheading:9551407-Muscle, Smooth, Vascular, pubmed-meshheading:9551407-Neutralization Tests, pubmed-meshheading:9551407-Paracrine Communication, pubmed-meshheading:9551407-Peptide Fragments, pubmed-meshheading:9551407-Peptides, pubmed-meshheading:9551407-Radioimmunoassay, pubmed-meshheading:9551407-Rats, pubmed-meshheading:9551407-Vasodilator Agents
pubmed:year
1998
pubmed:articleTitle
Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells.
pubmed:affiliation
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't