Full-length and truncated neurokinin-1 receptor expression and function during monocyte/macrophage differentiation. 2006

J-P Lai, and W Z Ho, and L E Kilpatrick, and X Wang, and F Tuluc, and H M Korchak, and S D Douglas
Division of Allergy and Immunology, The Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, and Department of Pediatrics, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.

The substance P (SP)-preferring receptor neurokinin-1 receptor (NK-1R) has two forms: a full-length receptor consisting of 407 aa and a truncated receptor consisting of 311 aa. These two receptors differ in the length of the C terminus of NK-1R. We studied the undifferentiated and phorbol myristate acetate (PMA)-differentiated human monocyte/macrophage cell line THP-1 to investigate the expression and function of NK-1R. The expression of full-length and truncated NK-1R in this cell line was determined by using real-time PCR and immunofluorescence staining. Undifferentiated THP-1 cells expressed only truncated NK-1R. The differentiation of THP-1 cells with PMA to a macrophage-like phenotype resulted in the expression of full-length NK-1R, which was functionally accompanied by an SP (10(-6) M)-induced Ca2+ increase. In contrast, the addition of SP (10(-6) M) did not trigger Ca2+ response in undifferentiated THP-1 cells; however, SP did enhance the CCR5-preferring ligand RANTES (CCL5)-mediated Ca2+ increase. When a plasmid containing the full-length NK-1R was introduced into undifferentiated THP-1 cells, exposure to SP triggered Ca2+ increase, demonstrating that the full-length NK-1R is required for SP-induced Ca2+ increase. The NK-1R antagonist aprepitant (Emend, Merck) inhibited both the SP-induced Ca2+ increase in PMA-differentiated THP-1 cells and the SP priming effect on the CCL5-mediated Ca2+ increase, indicating that these effects are mediated through the full-length and truncated NK-1R, respectively. Taken together, these observations demonstrate that there are unique characteristics of NK-1R expression and NK-1R-mediated signaling between undifferentiated THP-1 cells and THP-1 cells differentiated to the macrophage phenotype.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013373 Substance P An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. Euler-Gaddum Substance P,Hypothalamic Substance P,SP(1-11),Euler Gaddum Substance P,Substance P, Euler-Gaddum,Substance P, Hypothalamic
D013755 Tetradecanoylphorbol Acetate A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA. Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer
D018040 Receptors, Neurokinin-1 A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells. NK-1 Receptors,Neurokinin-1 Receptors,Receptors, Substance P,SP-P Receptors,Substance P Receptors,NK-1 Receptor,Neurokinin-1 Receptor,Receptors, NK-1,Receptors, SP-P,SP-P Receptor,Substance P Receptor,Substance-P Receptor,Tachykinin Receptor 1,NK 1 Receptor,NK 1 Receptors,Neurokinin 1 Receptor,Neurokinin 1 Receptors,P Receptor, Substance,P Receptors, Substance,Receptor, NK-1,Receptor, Neurokinin-1,Receptor, SP-P,Receptor, Substance P,Receptor, Substance-P,Receptors, NK 1,Receptors, Neurokinin 1,Receptors, SP P,SP P Receptor,SP P Receptors

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