Potency, efficacy, and selectivity of GR64349 at human recombinant neurokinin NK2 and NK1 receptors.
Neurosci Lett
; 711: 134456, 2019 10 15.
Article
em En
| MEDLINE
| ID: mdl-31445972
ABSTRACT
The affinity, potency, efficacy, and selectivity of the NK2 receptor agonist GR64349 ([Lys3,Gly8,-R-γ-lactam-Leu9]NKA(3-10)) at human recombinant NK2 and NK1 receptors was examined. In radioligand binding studies, GR64349 displaced [125I]-NKA binding to NK2 receptors with high affinity (pKi 7.77â¯+â¯0.10) but only weakly displaced [3H]-septide binding to NK1 receptors (pKi <5). In functional studies examining increases in intracellular inositol-1 phosphate (IP-1) accumulation, calcium levels, and cyclic AMP synthesis, GR64349 was a full agonist by reference to the endogenous agonists NKA (NK2 receptors) and substance P (NK1 receptors). GR64349 increased IP-1 accumulation with 1,400-fold greater potency in cells expressing NK2 receptors (pEC50 9.10â¯+â¯0.16) than cells expressing NK1 receptors (pEC50 5.95â¯+â¯0.80). For calcium responses, GR64349 was 500-fold more potent in the assay using NK2 receptors (pEC50 9.27 + 0.26) than NK1 receptors (pEC50 6.55â¯+â¯0.16). GR64349 also stimulated cyclic AMP synthesis in both cell lines, and was almost 900-fold more potent at NK2 receptors (pEC50 10.66â¯+â¯0.27) than NK1 receptors (pEC50 7.71â¯+â¯0.41). These findings confirm that GR64349 is the most selective NK2 receptor agonist described to date.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores da Neurocinina-2
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Receptores da Neurocinina-1
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article