Septide and neurokinin A are high‐affinity ligands on the NK‐1 receptor: evidence from homologous versus heterologous binding analysis

FEBS Letters

Hastrup, Hanne¹  Schwartz, Thue W.¹ 

[1] Laboratory for Molecular Pharmacology, Rigshospitalet 6321, DK-2100 Copenhagen, Denmark

关键词: Substance P;    Neurokinin A;    Septide;    7TM receptor;    Neuropeptide;    Ligand binding;   

DOI  :  10.1016/S0014-5793(96)01337-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The three main tachykinins, substance P, neurokinin A (NKA), and neurokinin B, are believed to be selective ligands for respectively the NK-1, NK-2 and NK-3 receptors. However, NKA also has actions which cannot be mediated through its normal NK-2 receptor and the synthetic peptide [pGlu⁶,Pro⁹]-Substance P^9–11 — called septide — is known to have tachykinin-like actions despite its apparent lack of binding to any known tachykinin receptor. In the cloned NK-1 receptor expressed in COS-7 cells NKA and septide as expected were poor competitors for radiolabeled substance P. However, by using radiolabeled NKA and septide directly, it was found that both peptides in homologous binding assays as well as in competition against each other in fact bound to the NK-1 receptor with high affinity: K _d values of 0.51 ± 0.15 nM (NKA) and 0.55 ± 0.03 nM (septide). It is concluded that NKA and septide are high-affinity ligands for the NK-1 receptor but that they are poor competitors for substance P, which in contrast competes very well for binding with both NKA and septide.

【 授权许可】

Unknown