Linked Life Data

8218295

Source:http://linkedlifedata.com/resource/pubmed/id/8218295

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
1993-12-21
pubmed:abstractText
Maternal-facing brush border membranes prepared from normal term human placentas possess the norepinephrine transporter. We investigated the interaction of nisoxetine with the human norepinephrine transporter by examining the binding of this ligand to the placental brush border membranes. Scatchard analysis revealed that nisoxetine bound with high affinity to a single class of binding sites in the membranes (dissociation constant = 13.8 +/- 0.4 nM). This value obtained from equilibrium experiments matched the value (11.2 nM) which was calculated using the association and dissociation rate constants. The maximal binding capacity (Bmax) was 5.1 +/- 0.1 pmol/mg of protein. The binding exhibited an absolute requirement for Na+ as well as Cl-. Presence of these ions enhanced the binding affinity without affecting Bmax. Kinetic analyses revealed that the coupling ratio of Na+/nisoxetine was 2, whereas the coupling ratio of Cl-/nisoxetine was 1. The binding was most potently inhibited by the ligands of the norepinephrine transporter (desipramine and nomifensine). The ligands of the serotonin transporter (imipramine, paroxetine, and fluoxetine) showed intermediate inhibitory potencies, whereas the ligands of the dopamine transporter (bupropion and GBR 12909) were the least potent. Among the monoamines, dopamine was the most potent inhibitor, followed by norepinephrine and serotonin. Though both cocaine and its analog RTI-55 were powerful inhibitors of the binding, RTI-55 was approximately 150 times more effective than cocaine. The inhibition of binding by norepinephrine, cocaine, and RTI-55 was competitive. Uptake of norepinephrine measured in membrane vesicles was found to be inhibited by treatment of the vesicles with phenylarsine oxide, a reagent specific for vicinal dithiol groups.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12178-85
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Sodium- and chloride-dependent, cocaine-sensitive, high-affinity binding of nisoxetine to the human placental norepinephrine transporter.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.