Linked Life Data

10342877

Source:http://linkedlifedata.com/resource/pubmed/id/10342877

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-6-3
pubmed:abstractText
Intracellular cAMP regulates cell proliferation as a second messenger of extracellular signals in a number of cell types. We investigated, by pharmacological means, whether an increase in intracellular cAMP levels changes proliferation rates of lactotrophs in primary culture, whether there are interactions between signal transduction pathways of cAMP and the growth factor insulin, and where the dopamine receptor agonist bromocriptine acts in the cAMP pathway to inhibit lactotroph proliferation. Rat anterior pituitary cells, cultured in serum-free medium, were treated with cAMP-increasing agents, followed by 5-bromo-2'-deoxyuridine (BrdU) to label proliferating pituitary cells. BrdU-labeling indices indicative of the proliferation rate of lactotrophs were determined by double immunofluorescence staining for PRL and BrdU. Treatment with forskolin (an adenylate cyclase activator) or (Bu)2cAMP (a membrane-permeable cAMP analog) increased BrdU-labeling indices of lactotrophs in a dose- and incubation time-dependent manner. The cAMP-increasing agents were also effective in increasing BrdU-labeling indices in populations enriched for lactotrophs by differential sedimentation. The stimulatory action of forskolin was observed, regardless of concentrations of insulin that were added in combination with forskolin. Inhibition of the action of endogenous cAMP by H89 or KT5720, a protein kinase A inhibitor, attenuated an increase in BrdU-labeling indices by insulin treatment. On the other hand, the specific mitogen-activated protein kinase inhibitor PD98059, which was effective in blocking the mitogenic action of insulin, markedly suppressed the forskolin-induced increase in BrdU-labeling indices. (Bu)2cAMP antagonized not only inhibition of BrdU labeling indices but also changes in cell shape induced by bromocriptine treatment, although forskolin did not have such an antagonizing effect. These results suggest that: 1) intracellular cAMP plays a stimulatory role in the regulation of lactotroph proliferation; 2) cAMP and insulin/mitogen-activated protein kinase signalings require each other for their mitogenic actions; and 3) the antimitogenic action of bromocriptine is, at least in part, caused by inhibition of cAMP production.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2850-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10342877-Animals, pubmed-meshheading:10342877-Bromocriptine, pubmed-meshheading:10342877-Bucladesine, pubmed-meshheading:10342877-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:10342877-Cell Division, pubmed-meshheading:10342877-Cells, Cultured, pubmed-meshheading:10342877-Cyclic AMP, pubmed-meshheading:10342877-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:10342877-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:10342877-Dose-Response Relationship, Drug, pubmed-meshheading:10342877-Female, pubmed-meshheading:10342877-Flavonoids, pubmed-meshheading:10342877-Forskolin, pubmed-meshheading:10342877-Insulin, pubmed-meshheading:10342877-Pituitary Gland, Anterior, pubmed-meshheading:10342877-Rats, pubmed-meshheading:10342877-Rats, Wistar
pubmed:year
1999
pubmed:articleTitle
Mitogen-activated protein kinase-dependent stimulation of proliferation of rat lactotrophs in culture by 3',5'-cyclic adenosine monophosphate.
pubmed:affiliation
Department of Physiology, Yamanashi Medical University, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't