Identification in the NK1 tachykinin receptor of a domain involved in recognition of neurokinin A and septide but not of substance P

FEBS Letters

Frobert, Yveline¹  Couraud, Jean-Yves¹  Grassi, Jacques¹  Wijkhuisen, Anne¹  Sagot, Marie-Astrid¹  Créminon, Christophe¹  Boquet, Didier¹ 

[1] CEA, Service de Pharmacologie et d'Immunologie, DSV/DRM, Bât. 136, CE Saclay, 91191 Gif-sur-Yvette Cedex, France

关键词: NK1 receptor;    Substance P;    Neurokinin A;    Septide;    Tachykinin;    Hydropathic complementarity;   

DOI  :  10.1016/S0014-5793(99)00298-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The three mammalian tachykinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), exert their physiological effects through specific receptors, NK1, NK2 and NK3, respectively. However, homologous binding studies have recently demonstrated that, contrary to the generally accepted belief, NKA could bind NK1 receptor with high affinity (Hastrup and Schwartz, 1996). Using COS-7 cells expressing the human NK1 receptor, we show that two simultaneous point mutations (E193L and V195R) in a restricted five amino acid sequence (the (193–197) region), selected because of its hydropathic complementarity with the common C-terminal extremity of tachykinins, abolish both the high-affinity binding and highly potent biological activity of NKA, without affecting those of SP. In addition, the same mutations also suppressed the high functional activity of septide, a synthetic SP atypical agonist ([pGlu⁶-Pro⁹] SP 6–11). These results suggest that the (193–197) region, located at the end of the second extracellular loop of the receptor, could be part of a common high-affinity binding domain for both NKA and septide, distinct from the SP binding site.

【 授权许可】

Unknown