Linked Life Data

17506596

Source:http://linkedlifedata.com/resource/pubmed/id/17506596

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-5-17
pubmed:abstractText
The normal function of retinal capillaries to distribute blood within the retina depends on appropriate contractility of retinal pericytes, which is thought to be modulated by agents that alter intracellular cyclic adenosine-3'-monophosphate (cAMP) levels. We examined the hypothesis that the vasoactive peptides Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase Activating Peptide (PACAP) reduce pericyte contractility via a protein kinase A (PKA)-mediated intracellular pathway that utilises cAMP. We utilised a single-call assay of contractility that is based on visualising the contractile force exerted by the pericytes on a silicone elastomer substrate and quantified, as a contractility index, from the number and length of wrinkles induced in the silicone elastomer by the pericytes. Pericytes were cultured from the retinas of freshly killed abattoir cattle, and identified in culture using immunohistochemical techniques. The pericytes contracted in response to norepinephrine (EC(50)=8 microM) and relaxed in response to both VIP (EC(50)=48 nM) and PACAP (EC(50)=3 nM). The relaxation induced by PACAP was inhibited by Rp-cAMPS (EC(50)=26 microM), which is an agent that inhibits cAMP binding at PKA. We confirmed the activation of PKA by PACAP in experiments where H89 also inhibited the PACAP-induced relaxation. U71322, which inhibits phospholipase C-linked events, was also able to inhibit the PACAP-induced pericyte relaxation. Our results support the hypothesis that PACAP leads to the relaxation of pericytes via a PKA-mediated intracellular pathway and a phospholipase C-mediated pathway, which probably relies on hyperpolarisation because of activation of Ca(2+)-dependent potassium channels. This single-cell assay has proved useful as the basis for the development of a diagnostic procedure for diabetic retinopathy, which is an eye disease caused by abnormal regulation of blood flow in the retinal capillaries.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1751-8741
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
44-51
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Contractility of retinal pericytes grown on silicone elastomer substrates is through a protein kinase A-mediated intracellular pathway in response to vasoactive peptides.
pubmed:affiliation
University of Technology, Faculty of Science, Sydney, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't