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

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 pretreatment with the selective NK2 receptor agonist, SR 48968 (2 nmol). Unlike NKA, the selective NK2 receptor agonists, (beta Ala(8)) NKA 4-10 and (NLeu(10)) 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. (c) 2012 Elsevier Ltd. All rights reserved.