Are biological actions of neurokinin A in the adult brain mediated by a cross-talk between the NK₁ and NK₂ receptors?

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• 作者：Ulrike Tauer ; Yi Zhao ; Steven P. Hunt ; Juraj Culman
• 关键词：Neurokinin A ; NK1/NK2 receptor interaction ; Brain ; Mouse
• 刊名：Neuropharmacology
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：63
• 期：6
• 页码：958-965
• 全文大小：706 K

文摘

Mice lacking the NK₁ receptor (NK₁R?/? mice) and selective, high-affinity, non-peptide, NK₁, NK₂ and NK₃ receptor antagonists were used to identify the tachykinin receptor subtype(s) mediating the central responses induced by neurokinin A (NKA). The peptides, substance P (SP), NKA and senktide and the antagonists were injected intracerebroventricularly (ICV) through an implanted cannula. NKA (50?pmol) was as potent as SP (50?pmol) in inducing grooming behaviour (face washing and hind limb grooming) in wild-type mice, but both peptides failed to induce behavioural responses in NK₁R?/? mice. In wild-type mice, the NK₁ receptor antagonist, RP 67580 (2?nmol), effectively inhibited grooming behaviour elicited by SP, but was inactive against grooming induced by NKA, which in turn was abolished after pre-treatment with the selective NK₂ receptor agonist, SR 48968 (2?nmol). Unlike NKA, the selective NK₂ receptor agonists, (¦Â Ala⁸) NKA 4-10 and (NLeu¹⁰) NKA 4-10, injected ICV at doses of 50 or 100?pmol did not elicit any behavioural response in wild-type mice. The NK₃ receptor antagonist, SR 142801, inhibited behaviours induced by the NK₃ receptor agonist, senktide, but did not alter behavioural responses to either SP or NKA in wild-type mice. The present findings demonstrate that central biological actions of SP and senktide are mediated by activation of NK₁ and NK₃ receptors, respectively. Our results also indicate that NK₁ receptors are essential for generating central actions induced by NKA, which are most probably mediated by a cross-talk between the NK₁ and NK₂ receptors.