Disease relevance of Tacr2

• Pulmonary NK2R mRNA expression was found to be reduced during acute pancreatitis and CP96,345 treatment normalized this reduction [1].
• Treatment of these mice with a neurokinin (NK)-1/NK-2 receptor antagonist, but not with anti-IL-5 antibodies, reduced their hypersensitivity [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].

High impact information on Tacr2

• Addition of a neutralizing substance P Ab or a neurokinin (NK)-1 receptor antagonist, but not an NK-2 receptor antagonist, dose-dependently prevented the RBL activation that resulted as a consequence of neural activation by either bradykinin or scorpion venom [4].
• Neurokinin-2 receptor (NK2R) mRNA expression was not detected in normal pancreas [1].
• 3. SR48968, NK2 receptor antagonist, did not modify the spontaneous activity and reduced the contractile effects induced by tachykinins without affecting the relaxation [5].
• SR48968, NK2 receptor antagonist, but not SR140333, NK1 receptor antagonist, decreased the tone only in mdx gastric preparations [6].
• Substance P induction of murine keratinocyte PAM 212 interleukin 1 production is mediated by the neurokinin 2 receptor (NK-2R) [7].

Anatomical context of Tacr2

• Immunohistochemistry demonstrated a consistent reduction of nNOS and NK2 receptor expression in mdx stomach smooth muscle cells and no change in nNOS and NK1 receptor expression in neurones [6].
• SP augmented the expression of PAM 212 keratinocyte IL-1alpha mRNA in a dose and time dependent manner and this induction was inhibited by an NK-2R antagonist [7].

Associations of Tacr2 with chemical compounds

• Similarly, MEN 10627 (pA2 9.20) is more active than R 396 (pA2 6.21), suggesting that the mouse NK2 receptor is similar to that of the rabbit [8].
• [beta-Ala(8)]-NKA(4-10), an NK2 receptor agonist, induced SR48968-sensitive contractions in both types of preparations, although the maximal response of mdx tissues was significantly lower than normal preparations [6].
• The NK2 receptor antagonist, MEN-10,376 and pretreatment with neurokinin A antiserum did not alter the behavioural effect of nociceptin [9].
• NK1 receptor antagonists such as RP 67580 (ED50:0.19 mg/kg, i.v.), spantide II (ED50:0.33 mg/kg, i.v.), and GR 82334 (ED50:0.26 mg/kg, i.v.), inhibited capsaicin-induced ear oedema, whereas SR 48968 (2.0 mg/kg, i.v.), a NK2 receptor antagonist, had no effect [10].
• 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) [11].

Regulatory relationships of Tacr2

• By contrast, NK-2R inhibition significantly enhanced the ACD response in NK-1R null or in wild-type mice, whereas epicutaneous application of NK-2R agonists diminished the ACD inflammation [12].
• Correspondingly, the addition of SP to these cells resulted in a rapid increase in intracellular Ca2+ levels that could be specifically blocked by an NK-2R antagonist [7].

Analytical, diagnostic and therapeutic context of Tacr2

• 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 [13].

References