Crosstalk between neurokinin receptors is relevant to hematopoietic regulation: cloning and characterization of neurokinin-2 promoter

Abstract

Neurokinin (NK)-1 and NK-2 receptors regulate hematopoiesis by interacting with neurotransmitters that belong to the tachykinin. This report studies the relationship between NK-1 and NK-2 in primary human bone marrow (BM) stroma, which supports hematopoiesis. Use of NK receptor antagonists and deficient stromal cells indicate that the neurotransmitter, substance P (SP), could exert dual hematopoietic effects (inhibitory or stimulatory), depending on the interacting receptor and crosstalk between NK-1 and NK-2. Cloning and identification of the minimal promoter for NK-2 and comparison with NK-1 promoter showed that the hematopoietic functions of NK receptors involve receptor crosstalk and the particular cytokine (IL-3, GM-CSF, TGF-beta or IL-1alpha). Crosstalk between NK-1 and NK-2 adds to communication within neural-hematopoietic axis.