Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1985-7-17
|
| pubmed:abstractText |
5-Methoxytryptoline potently inhibits [3H]imipramine binding to membranes from the cerebral cortex and platelets. Since 5-methoxytryptoline, which appears to occur endogenously with particularly high levels in the human pineal gland, also inhibits 5-hydroxytryptamine (5-HT, serotonin) uptake, it should be considered as a putative endogenous ligand modulating 5-HT transport. As the 5-HT transporter complex comprises the imipramine and the substrate recognition sites, which interact allosterically, it was essential to define the mechanism of inhibition of [3H]imipramine binding by 5-methoxytryptoline. Human platelets show an active and saturable uptake of 5-HT and tryptamine. The uptake of both substrates appears to be mediated by the same carrier and it is inhibited by 5-methoxytryptoline at submicromolar concentrations. 5-HT and tryptamine inhibit [3H]imipramine binding in human platelets with a Hill slope for inhibition close to unity and IC50 values of 3,265 and 3,475 nM, respectively. This inhibition is, however, not competitive because both 5-HT and tryptamine significantly decrease the rate of [3H]imipramine-receptor dissociation. Although 5-methoxytryptoline potently inhibits [3H]imipramine binding (IC50 = 44 nM) in human platelets with a Hill slope of unity, it does not affect the receptor-ligand dissociation rate of [3H]imipramine even at concentrations up to 100 microM. The present experiments show that 5-methoxytryptoline, in spite of its chemical similarity to the indoleamine transporter substrates, interacts with the imipramine receptor through a mechanism of competitive inhibition. This conclusion is supported by a selective effect of 5-methoxytryptoline on the Kd of [3H]imipramine binding.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-hydroxytryptoline,
http://linkedlifedata.com/resource/pubmed/chemical/Carbolines,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Desipramine,
http://linkedlifedata.com/resource/pubmed/chemical/Imipramine,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurotransmitter,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Tryptamines,
http://linkedlifedata.com/resource/pubmed/chemical/imipramine receptor,
http://linkedlifedata.com/resource/pubmed/chemical/tryptamine,
http://linkedlifedata.com/resource/pubmed/chemical/tryptoline
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0022-3042
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
45
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
249-56
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:2987413-Binding, Competitive,
pubmed-meshheading:2987413-Blood Platelets,
pubmed-meshheading:2987413-Carbolines,
pubmed-meshheading:2987413-Carrier Proteins,
pubmed-meshheading:2987413-Desipramine,
pubmed-meshheading:2987413-Humans,
pubmed-meshheading:2987413-Imipramine,
pubmed-meshheading:2987413-Indoles,
pubmed-meshheading:2987413-Receptors, Drug,
pubmed-meshheading:2987413-Receptors, Neurotransmitter,
pubmed-meshheading:2987413-Serotonin,
pubmed-meshheading:2987413-Tryptamines
|
| pubmed:year |
1985
|
| pubmed:articleTitle |
5-Methoxytryptoline, a competitive endocoid acting at [3H]imipramine recognition sites in human platelets.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|