Linked Life Data

12132928

Source:http://linkedlifedata.com/resource/pubmed/id/12132928

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2002-7-22
pubmed:abstractText
Intracellular Ca(2+) plays an important role in signal transduction, and we are developing new MRI techniques to study its regulation in living animals. We have reported on an MRI contrast agent (DOPTA-Gd) where the relaxivity of the complex is controlled by the presence or absence of the divalent ion Ca(2+). By structurally modulating inner-sphere access of water to a chelated Gd(3+) ion, we observe a substantial and reversible change in T(1) upon the addition of Ca(2+) and not other divalent ions. Luminescence lifetime and NMRD measurements of the complex have been acquired, and several parameters contribute to the Ca(2+) dependent relaxivity change of DOPTA-Gd. The number of inner-sphere water molecules is more than doubled after the Ca(2+) concentration is increased. This finding strongly supports the proposed conformational change of DOPTA-Gd when Ca(2+) is bound. Relaxometric measurements confirm these results and provide an indication that second-sphere water molecules are probably responsible for paramagnetic relaxation enhancement in the absence of Ca(2+). After Ca(2+) is bound to DOPTA-Gd, the molecule undergoes a substantial conformational change that opens up the hydrophilic face of the tetraazacyclododecane macrocycle. This change dramatically increases the accessibility of chelated Gd(3+) ion to bulk solvent. The design of this class of calcium-activated MR contrast agent was based primarily on the assumption that the number of coordinated inner-sphere water molecules would be the dominating factor in observed relaxivity measurements. This result has been confirmed; however, careful mechanistic studies reveal that additional factors are involved in this process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0020-1669
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4018-24
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Mechanistic studies of a calcium-dependent MRI contrast agent.
pubmed:affiliation
Division of Biology, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't