Disease relevance of Tac4

• CONCLUSION: These data suggest that tachykinin NK1 receptors do not affect allergic airway inflammation or endogenous substance P content of alveolar macrophages but influence baseline responsiveness and promote features of remodeling such as goblet cell hyperplasia [1].
• The tachykinin neurokinin B (NKB) has been implicated in the hypertension that characterises pre-eclampsia, a condition where tissue oedema is also observed [2].
• Tachykinin NK2 receptor antagonists could reduce motility and symptoms during gastrointestinal diseases characterized by local inflammation such as diarrhea or colitis; however, how these conditions change pharmacodynamic and pharmacokinetic characteristics of NK2 receptor antagonists is unknown [3].
• The results suggest that clinical trials of tachykinin NK1 antagonists for the treatment of itching in atopic dermatitis patients would be warranted [4].
• Thus, we examined the effect of a tachykinin NK1 antagonist, BIIF 1149 CL, on scratching behaviour in a picrylchloride-induced dermatitis model in NC/Nga mice [4].

Psychiatry related information on Tac4

• RATIONALE: It has been suggested that tachykinin NK(2) receptor antagonists may have therapeutic utility in anxiety and/or depressive disorders [5].
• The tachykinin system therefore may play an important role in the regulation of emotional states and the development of anxiety disorders and depression [6].

High impact information on Tac4

• Opioid and tachykinin systems are involved in modulation of pain transmission in the spinal cord [7].
• HK-1 has several biological activities that are similar to the most studied tachykinin, substance P, such as induction of plasma extravasation and mast cell degranulation [8].
• Tachykinin 4 gene expression was detected primarily in adrenal gland and in the placenta, where, like neurokinin B, significant amounts of EKB-like immunoreactivity were detected [9].
• T-cell developmental blockage by tachykinin antagonists and the role of hemokinin 1 in T lymphopoiesis [10].
• (4) Tooth development in explant cultures is blocked both by tachykinin-precursor-specific antisense oligonucleotide and by an SP receptor antagonist: in both cases the block is relieved by exogenous SP [11].

Chemical compound and disease context of Tac4

• In contrast, treatment with the tachykinin NK2 receptor antagonist SR48968 did not affect the dinitrofluorobenzene-induced hypersensitivity reaction [12].
• Role of central and peripheral tachykinin NK1 receptors in capsaicin-induced pain and hyperalgesia in mice [13].
• 5. Amyloid beta-peptide toxicity was inhibited by the concurrent treatment of the cells with the tachykinin physalaemin with an ED50 of 10(-6) M [14].

Biological context of Tac4

• Lack of a significant effect of deletion of the tachykinin neurokinin-1 receptor on wound healing in mouse skin [15].
• Nepadutant pharmacokinetics and dose-effect relationships as tachykinin NK2 receptor antagonist are altered by intestinal inflammation in rodent models [3].
• Our results demonstrate that substance P may modulate intestinal motility by acting on the interstitial cells of Cajal by activating nonselective cation channels via the release of intracellular Ca2+ induced by tachykinin NK1 receptor stimulation [16].
• Overall the results indicate that MEN15596 is a potent and selective tachykinin NK(2) receptor antagonist possessing high affinity and potency for guinea-pig, pig and human receptor, long duration of action in in vivo experiments and good oral bioavailability [17].
• Further evidence for the presence of "septide-sensitive" tachykinin binding sites in tissues possessing solely NK(1) tachykinin receptors [18].

Anatomical context of Tac4

• Immunohistochemistry for substance P, a substance P enzyme immunoassay, and catecholamine histofluorescence indicated that both tachykinin-containing sensory fibers and sympathetic fibers were increased around the airways of CCSP-NGF mice [19].
• There was preferential expression of PPT-C mRNA in dendritic cell subpopulations that were CD11b+, but not B220+ or GR-1+ [20].
• The activation of tachykinin NK receptors by neuropeptides may induce the recruitment of eosinophils in vivo [21].
• 6. These results suggest that both tachykinin NK1 receptors and sensory nerves are involved in the development of vascular hyperpermeability changes found in the trachea of DNFB-sensitized mice after a repeated DNS-challenge [22].
• Here we demonstrate the expression of mouse PPT-C mRNA by CD11b+ macrophages, CD11c+ dendritic cells and in the microglial cell line EOC 13.31 [20].

Associations of Tac4 with chemical compounds

• Treatment of CCSP-NGF mice with the sympathetic-specific neurotoxin 6-hydroxydopamine (6-OHDA) eliminated the sympathetic component of the airway innervation, leaving a specific hyperinnervation by tachykinin-containing sensory fibers [19].
• The affinity of the non-peptide antagonist CP-96,345 for tachykinin NK1 receptors has been estimated in a range of species by use of both radioligand binding and functional assays [23].
• We studied the role of tachykinin receptors in mice that were skin-sensitized with dinitrofluorobenzene (or vehicle) and challenged intranasally with dinitrobenzene sulfonic acid [12].
• Finally, while several tachykinins and tachykinin-related compounds stimulated cAMP formation or increased inositol phosphate accumulation in CHO-rat-NK1 cells, these compounds only increased the accumulation of inositol phosphates in the two other preparations [18].
• An N-methyl-D-aspartate-receptor antagonist but not a tachykinin-NK1-receptor antagonist produced greater antinociception in vincristine-treated mice [24].

Other interactions of Tac4

• In the lungs, the antagonist was found to suppress the increase in SP concentration, PPT-A mRNA expression and preprotachykinin-C gene (PPT-C) mRNA expression [25].
• However, the mRNAs of PPT-B, PPT-C and NEP appeared in blastocyst-stage embryos [26].

Analytical, diagnostic and therapeutic context of Tac4

• Tachykinin NK1 receptor blockade, by treatment with the antagonist RP67580, or absence of the tachykinin NK1 receptor resulted in a strong reduction in the accumulation of neutrophils in the bronchoalveolar lavage fluid, and in the development of tracheal hyperreactivity in mice 48 h after challenge [12].
• Triiodothyronine markedly decreased anterior pituitary tachykinins, but ovariectomy and estrogen administration failed to significantly affect tachykinin concentrations in the anterior pituitary of transgenic mice [27].
• CONCLUSIONS: Because millimolar concentrations of local anesthetics are within the range measured in spinal cord during intrathecal and epidural procedures, these results are consistent with a direct action of local anesthetics on tachykinin-mediated neurotransmission during regional anesthesia [28].

References