Linked Life Data

12630816

Source:http://linkedlifedata.com/resource/pubmed/id/12630816

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2003-3-12
pubmed:abstractText
The expression of components of the adrenomedullin (AM) system (AM and its receptors) has been detected in mammalian adrenal zona glomerulosa (ZG) cells, and evidence has been provided that AM is able to inhibit agonist-stimulated aldosterone secretion from and to enhance the proliferative activity of ZG cells. However, there has been no evidence that the endogenous AM system acts as a physiological regulator of ZG function. Hence, we investigated whether the suppression of AM gene transcription by a specific antisense oligodeoxynucleotide (ODN) is able to alter the secretion and growth of rat ZG cells cultured in vitro. ZG cell cultures were examined 0, 2, 4, 6 and 8 days after treatment with scrambled sense (S)-ODN (control cultures) and AM antisense (A)-ODN. Control cultures, as well as freshly dispersed ZG cells and ODN-untreated cultures, expressed AM as mRNA and protein. A-ODN treatment suppressed AM expression within 4 days and the suppression lasted until day 6. Confluent control cultures displayed basal and angiotensin-II (Ang-II), K(+)- and adrenocorticotropic hormone (ACTH)-stimulated aldosterone secretions similar to those of ODN-untreated cultures. A-ODN treatment magnified the aldosterone response to Ang-II and K+ at days 4 and 6 (but not at day 8), without affecting the basal or ACTH-stimulated secretion. As compared to ODN-untreated and control cultures, non-confluent A-ODN-treated ones showed a 40% elongation in the duplication time, a significant decrease in the proliferation index, and a marked rise in apoptotic index from day 4 to day 8. In conclusion, our study validates the use of A-ODN to block the endogenous AM system, showing that suppression of AM-synthesis requires at least 2 days to become appreciable and persists for at least 6 days. Moreover, it provides the first evidence that endogenous AM plays a physiological role in cultured rat ZG cells, by exerting a buffering action on their acute secretory response to Ang-II and K+ and by maintaining normal basal proliferative and apoptotic activities.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0916-9636
pubmed:author
pubmed:issnType
Print
pubmed:volume
26 Suppl
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S85-92
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Role of the endogenous adrenomedullin system in regulating the secretion and growth of rat adrenal cortex.
pubmed:affiliation
Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy.
pubmed:publicationType
Journal Article