Disease relevance of Tacr3

• To determine how the profile of NK receptor expression changes in murine CD8(+) T cells as they respond to intracellular pathogens, we used class I tetramer reagents to directly examine Ag-specific T cells during lymphocytic choriomeningitis virus and Listeria monocytogenes infections [1].
• NK cells from adult Csf1(op)/Csf1(op) mice expressed normal levels of Ly49.Maturation of the NK receptor repertoire is a slow process regardless of their stem cell origin or reduced marrow space caused by osteopetrosis [2].

High impact information on Tacr3

• The NKR alteration was selective for NK cells and did not result in a resistance to lysis in general; NKR and NKS variants were equally susceptible to (i) cytolysis mediated by alloimmune or lectin-dependent effector T cells and (ii) antibody- and complement-mediated lysis [3].
• These results are compatible with the hypothesis that the NKR variants have an altered acceptor site on the target cell membrane that normally binds the "lytic moiety" delivered by the effector cell [3].
• Cytolysis of both NKR and NKS lines was mediated by nylon-nonadherent asialo-GM1+ effector cells, and effectors from poly(I) . poly(C)-boosted mice preferentially lysed the NKS lines [3].
• The aim of this study was to determine whether chimeric NK-receptor-bearing T cells would directly kill tumor cells and lead to induction of host immunity against tumors [4].
• Role of a NK receptor, KLRE-1, in bone marrow allograft rejection: analysis with KLRE-1-deficient mice [5].

Biological context of Tacr3

• Prevention of activation and expansion of the potentially autoreactive CTLA-4(-/-) T cells by the Ly49A-mediated inhibitory signal demonstrates that NKR expression can play an important regulatory role in T-cell homeostasis in vivo [6].
• In an attempt to understand potential novel functions of receptors in vivo, we evaluated gene expression after cross-linking the activating Ly-49D mouse NK receptor [7].
• In contrast, IRF-2-deficient NK cells in bone marrow (BM) showed relatively mature phenotypes (CD11b(low)Dx5(high)) with less compromised NK receptor repertoire [8].
• Experimental infection in mice has revealed that the genetically determined natural resistance to murine CMV (MCMV) may be mediated either by direct recognition between the NK receptor Ly49H and the pathogen-encoded glycoprotein m157 or by epistatic interaction between Ly49P and the host MHC H-2D(k) [9].
• RAI genes include olfactory receptor genes [3], and the various genes encoding antigen receptors on lymphocytes (immunoglobulin genes, T cell receptor genes and NK receptor genes [4] [5] [6] [7]) [10].

Anatomical context of Tacr3

• These results suggest that the behavioural response to NK-2 and NK-3 receptor agonists may be partially inhibited by spantide through the activation of opioid system in the mouse spinal cord [11].
• Neither tachykinin NK2 nor NK3 receptor antagonists suppressed eosinophil recruitment [12].
• By using a double immunofluorescence method we examined co-localization of neurokinin-3 receptor (NK-3R) and N-methyl-D-aspartate (NMDA)/alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits in neurons of the substantia nigra of adult mice [13].
• They also suggest the existence of a distinct neurokinin B receptor in the mouse spinal cord and the apparent identification of a third neurokinin receptor in the guinea-pig ileum [14].
• The co-expression of NK-3R and NMDA/AMPA receptor subunits in the nigral neurons has provided a structural basis for functional modulation of neuronal glutamate receptors by neurokinin-3, suggesting that neurokinin peptides may be involved in modulation of neuronal properties and excitotoxicity in the substantia nigra of basal ganglia [13].

Associations of Tacr3 with chemical compounds

• In addition, the [Ca2+]i increase by 0.33 microM senktide, an NK3 receptor agonist, was inhibited by SR 142801 but not by SR 48968 [15].
• In addition, NK2 and NK3 receptor-mediated [Ca2+]i increase was partially attenuated in the absence of extracellular Ca2+ or in the presence of nickel, an inorganic Ca2+ influx blocker, but was unaffected by nifedipine and omega-conotoxin, L- and N-type voltage-dependent Ca2+ channel blockers, respectively [15].
• Neuro-cutaneous interactions may be mediated by the release of neuropeptides such as substance P (SP) which activate immunocompetent cells in the skin by binding to high affinity neurokinin receptors (NKR) [16].
• Moreover, it seems unlikely that the NK3 receptor is involved primarily in capsaicin-induced mouse ear oedema [17].
• Significant GABA release was observed when striatal slices were challenged with the NK-3 receptor agonist senktide, the selectivity of which was confirmed using the NK-3 receptor antagonist SR142801 [18].

Regulatory relationships of Tacr3

• The specific NK1 receptor antagonist, RP67580 (10(-9) mol per mouse, i.v.) was the most effective in reducing the substance P-induced plasma extravasation when compared with other NK receptor antagonists, FK224 and FK888.(ABSTRACT TRUNCATED AT 250 WORDS)[19]

Other interactions of Tacr3

• Pretreatment with naloxone, an opioid antagonist, resulted in a reversible effect on the behavioural reduction of NK-2 and NK-3 receptor agonists produced by spantide [11].
• Neurokinin-3 receptor (NK3R) mRNA expression was absent in both pancreas and lung [20].
• Furthermore, the depolarization by 60 mM K+ did not affect the [Ca2+]i. These findings suggested that the NK2 and NK3 receptor-mediated [Ca2+]i increase was due to the activation of PLC and was dependent on the mobilization of internal Ca2+ and the entry of extracellular Ca2+ through voltage-independent channels [15].
• In contrast, these neurons exhibiting both NK-3R and GluR4 immunoreactivity were hardly detected although GluR4-positive neurons were still distributed in the substantia nigra [13].
• The antinociception caused by i.d. injection of the NK3 receptor antagonist SR 142801 against both phases of the formalin test, but not that of NK1 and NK2 receptor antagonists, was significantly reversed by intraperitoneal (i.p.) injection of naloxone (5 mg/kg) [21].

Analytical, diagnostic and therapeutic context of Tacr3

• Chimeric NK-receptor-bearing T cells mediate antitumor immunotherapy [4].

References