The neurokinin-1 (NK-1) and neurokinin-2 (NK-2) receptors are both members of the tachykinin receptor family. Although both receptors bind peptide ligands synthesized from common precursors and activate inositol 1,4,5- triphosphate and cAMP responses, differences between these receptors have been observed in the extent and kinetics of agonist-induced responses. Here, to test if structurally homologous domains of the NK-1 and NK-2 receptors are functionally distinct, stably transfected Chinese hamster ovary (CHO) cell lines expressing receptors that had either their putative third cytoplasmic loop (C3) or carboxyl tail (CT) domains replaced with the equivalent domain of the other receptor were compared with stably transfected CHO cell lines expressing wild-type receptors. Radioligand binding demonstrated that each of these chimeric receptors had agonist binding affinities indistinguishable from wild-type receptors. However, not all chimeric receptors were equivalent in their ability to stimulate inositol phospholipid turnover and cAMP production. The data suggest that the NK-1 C3 and the NK-2 CT domains play important roles in G-protein activation that cannot be replaced by the analogous domain of the other receptor. The characterization of CHO cell lines expressing truncated forms of both receptors supported the hypothesis that the CT domain of the NK-2, but not the NK-1, receptor plays a critical role in G-protein activation. The data suggest a potential mechanism for the differences observed in response characteristics in tissues expressing NK-1 and NK-2 receptors and demonstrate that the mechanisms whereby highly homologous receptors activate G-proteins can be different.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Biological Chemistry|
|State||Published - Jan 1 1993|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology