Disease relevance of Tac2

• Cutaneous allergic contact dermatitis responses are diminished in mice deficient in neurokinin 1 receptors and augmented by neurokinin 2 receptor blockage [1].
• These findings are in keeping with a role for NKB in mediating plasma extravasation in diseases such as pre-eclampsia [2].
• Several observations suggest that tachykinins (substance P, neurokinin A and neurokinin B) are involved in the pathogenesis of pulmonary diseases and elicit several airway responses such as bronchoconstriction and neurogenic inflammation via interactions with specific receptors denoted NK(1), NK(2) and NK(3) [3].
• Thus whereas behavioral hypersensitivity after injury is preserved in ppt-A -/- mice, our results suggest that the magnitude and duration of these behavioral responses would be reduced in the absence of SP and/or NKA [4].
• OBJECTIVE: The present study was designed to examine the effects of allergen sensitization and challenge on the SP/NKA expression in the jugular-nodose ganglion neurons innervating the murine airways [5].

Psychiatry related information on Tac2

• The effects of intracerebroventricular injections of the neurokinin-2 (NK-2) receptor agonist neurokinin A and the neurokinin-3 (NK-3) receptor agonist senktide on scopolamine (sc)-induced amnesia were investigated based on spontaneous alternation performance in mice [6].

High impact information on Tac2

• Neurogenic inflammation, which results from peripheral release of substance P and neurokinin A, is almost absent in the mutant mice [7].
• Thus, the behavioral manifestations of threshold changes in nociceptive processing in the setting of injury do not appear to require SP or NKA [8].
• These results indicate that the reduction of seizure activity and the neuroprotection observed in preprotachykinin A null mice are caused by the extinction of a SP/neurokinin A-mediated signaling pathway that is activated by seizures [9].
• We found that GATA-1 strongly activates transcription of the Tac-2 gene, which encodes proneurokinin-B, a precursor of neurokinin-B (NK-B) [10].
• Tac-2 was expressed in normal murine erythroid cells and was induced upon ex vivo erythropoiesis [10].

Biological context of Tac2

• The data show that the mRNAs of tachykinins (particularly NKB and HK-1), tachykinin receptors, and NEP are locally expressed in the mouse uterus, and their expression changes during the estrous cycle and during pregnancy [11].
• The contractile response to capsaicin or neurokinin A of the rat isolated bladder were significantly reduced by incubation with phenoxybenzamine at a concentration reported to produce a selective alkylation of neurokinin-2 receptors, while the response to substance P or KCl was unaffected [12].
• There was an eightfold increase in p38 MAPK phosphorylation after a 10-min incubation with ACh and a threefold increase with NKA [13].
• NKA and SP share the same amino acid sequence at their C-terminal active site domains but differ in structure at their N-terminal domains [14].
• The aim of this study was to elucidate the role of the neuromodulator substance P and its related tachykinin neurokinin A (NKA) in the homeostasis of respiratory activity [15].

Anatomical context of Tac2

• Local microinjections of NPK enhanced memory retention when injected into the rostral and caudal portions of the hippocampus (0.25 and 0.50 microgram) and the amygdala (1.0 microgram), but were without effect when injected into the septum and the caudate [16].
• Congruent distribution patterns of Tac2 mRNA and NKB were found in many nuclei of the thalamus and hypothalamus (habenula, anterodorsal nucleus, preoptic area, arcuate nucleus, paraventricular nucleus) [17].
• However, results of in situ hybridization experiments intimated that eosinophils produced predominantly preprotachykinin mRNAs which encode SP but are devoid of the SK/neuropeptide K sequence [18].
• These data suggest that endopeptidase-24.11 may be an important enzyme responsible for terminating of SP- or NK A-induced behavioral response at the spinal cord level [19].
• In rat duodenum and mouse bladder membranes, the binding of BHE was inhibited by substance K greater than kassinin greater than eledoisin greater than neuromedin K greater than substance P greater than physalaemin indicating the same receptor site as for BHSK [20].

Associations of Tac2 with chemical compounds

• The tachykinin NK(3) receptor-selective antagonist, SR 142801 (0.3 microM), had little effect on responses to SP and NKB [21].
• The tachykinin NK(2) receptor may also participate in the responses to NKA and NKB [21].
• SR48968 did not affect responses to SP or [Sar(9)Met(O(2))(11)]SP, but reduced the effect of higher concentrations of NKA and shifted the log concentration-response curve to NKB to the right [21].
• Neurokinin A (0.1-3 micrograms) or senktide (0.0003-0.03 microgram) alone did not influence either spontaneous alternation performance or total arm entries [6].
• The tachykinins neurokinin A and physalaemin stimulate murine thymocyte proliferation [22].

Regulatory relationships of Tac2

• The activity of neuromedin K was blocked by the substance P antagonist [D-Pro2D-Trp7.9]substance P at doses of antagonist which effectively blocked the activity of the other tachykinins [23].

Other interactions of Tac2

• Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function [24].
• We conclude that NKB is a potent stimulator of plasma extravasation through two distinct pathways: via activation of NK(1) receptors, and via a novel neurokinin receptor-independent pathway specific to NKB that operates in the mouse lung [2].
• SP proved to be the most efficient IL-2 inducer, exerting its maximal effect at concentrations that were 4 to 5 orders of magnitude lower than the optimal stimulatory concentrations of physalaemin, NKA, or NKB [25].
• Accordingly, mice showed no NKB in the projection areas of these nuclei, such as the olfactory tubercle, whereas a clear NKB signal was present in rat tissues [17].
• Characterization of the profile of neurokinin-2 and neurotensin receptor antagonists in the mouse defense test battery [26].

Analytical, diagnostic and therapeutic context of Tac2

• NKA, and to a lesser extent PHY, but none of the other tachykinins tested, displayed a stimulatory action in murine thymocyte cultures, utilised as an interleukin-1 (IL-1) bioassay [22].
• Because the antiserum K-12 recognizes various tachykinins, such as neurokinin A (100%), kassinin (103%), eledoisin (51%), neurokinin B (18%), physalaemin (0.7%), and substance P (0.7%), the immunoreactivity detected in this enzyme immunoassay has been termed TK-LI [27].
• Two mouse monoclonal antibodies, 11H9.1 and 1G7.10, raised against the COOH-terminus peptide (359-390) of the rat neurokinin-2 receptor, were used to visualize by light and electron microscope immunocytochemistry the distribution of this receptor in adult rat spinal cord [28].
• High-performance liquid chromatography (HPLC) fractions considered to represent neurokinin A, eledoisin and neuropeptide K were present in guinea-pig thymus but only the first two were present in rat thymus [29].
• To assess vasoreactivity in small arteries, precision cut lung slices were subjected to videomorphometry and the response to NKA was examined, which showed significantly stronger effects in the BDNF-transgenic mice, while NK-2 receptor mRNA expression, assayed by real-time RT-PCR, was reduced [30].

References