Linked Life Data

9022979

Source:http://linkedlifedata.com/resource/pubmed/id/9022979

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-5-5
pubmed:abstractText
The action of rotameric probes introduced either in position 7 or 8 in the sequence of substance P (SP) was investigated, i.e. L-tetrahydroisoquinoleic acid (Tic), L-fluorenylglycine (Flg), L-diphenylalanine (Dip), the diastereoisomers of L-1-Indanylglycine (Ing) and L-benz[f]indanylglycine (Bfi), the Z- and E-isomers of dehydrophenylalanine and dehydronaphthylalanine (delta ZPhe, delta EPhe, delta ZNal, ENal) and L-O,O'-dimethylphenylalanine (Dmp). The aim of this study was the topographical characterization of the binding subsites of human NK-1 receptor expressed in CHO cells, especially the S7 and S8 subsites, corresponding to residues Phe7 and Phe8 of substance P. According to the binding potencies of these substituted-SP analogues, the S7 binding subsite is smaller than the S8 subsite: the S7 subsite accepts only one aromatic nucleus, while the S8 can accommodate three coplanar nuclei altogether. These findings are compatible with the idea that the S8 binding subsite may reside in the extracellular loops of the hNK-1 receptor. NK-1 agonists bind to human NK-1 receptor and activate the production of both inositol phosphates and cyclic AMP. As already quoted for septide, [pGlu6, Pro9]SP(6-11), discrepancies are observed between affinity (K1) and activity (EC50) values for IPs production. While a weak correlation between K1 and EC50 values for IPs production could be found (r = 0.70), an excellent correlation could be demonstrated between their affinities (K1) and their potencies (EC50) for cAMP production (r = 0.97). The high potency (EC50) observed for "septide-like' molecules on PI hydrolysis, compared to their affinity is not an artefact related to the high level of NK-1 receptors expressed on CHO cells since a good correlation was found between EC50 values obtained for PI hydrolysis and those measured for spasmogenic activity in guinea pig ileum bioassay (r = 0.94).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2167-78
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Tachykinin NK-1 receptor probed with constrained analogues of substance P.
pubmed:affiliation
Laboratoire de Chimie Organique Biologique, CNRS URA 493, Université P. et M. Curie, Paris, France.
pubmed:publicationType
Journal Article, Comparative Study