Linked Life Data

3574288

Source:http://linkedlifedata.com/resource/pubmed/id/3574288

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1987-5-28
pubmed:abstractText
The properties of high affinity nicotine-binding sites in rat brain were studied by monitoring the kinetics of L-[3H]nicotine binding to whole brain membrane preparations, including both total membranes and membrane subfractions. Although nicotine appeared to bind to a single class of sites, with an apparent equilibrium dissociation constant of 2-3 nM, the binding kinetics were biphasic at all temperatures and at all nicotine concentrations tested. An initial rapid binding process, with an association rate constant of around 0.02 min-1 nM-1 at 0 degree, was followed by a slower binding process. Both the rate and the proportion of binding that occurred by the slower process were dependent on the nicotine concentration. By comparison, the kinetics of dissociation were first order at all concentrations, with a rate constant of 0.04 min-1 at 0 degree. The rates of both association and dissociation increased significantly with temperature, but there was no changed in the apparent affinity of the sites. The same results were obtained with several different membrane preparations, including whole brain membrane preparations, detergent-permeabilized membranes, P-2 fractions, and synaptosomes. The results were found to be consistent with a two-state model. Analyses based on this model indicate that the binding sites can assume two different conformations, one having a high affinity (KD = 1 nM) and the other a low affinity (KD = 150 nM) for nicotine. It was estimated that approximately 60% of the sites are in the low affinity conformation in the absence of ligand. However, the evidence suggests that nicotine binding can facilitate a shift in the conformational equilibrium, favoring the high affinity state.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
392-400
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Kinetics and mechanism of L-[3H]nicotine binding to putative high affinity receptor sites in rat brain.
pubmed:publicationType
Journal Article