title: Are biological actions of neurokinin A in the adult brain mediated by a cross-talk between the NK1 and NK2 receptors?
abstract: Mice lacking the NK(1) receptor (NK(1)R-/- mice) and selective, high-affinity, non-peptide, NK(1), NK(2) and NK(3) 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 NK(1)R-/- mice. In wild-type mice, the NK(1) 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 NK(2) receptor agonist, SR 48968 (2 nmol). Unlike NKA, the selective NK(2) receptor agonists, (β 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 NK(3) receptor antagonist, SR 142801, inhibited behaviours induced by the NK(3) 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 NK(1) and NK(3) receptors, respectively. Our results also indicate that NK(1) receptors are essential for generating central actions induced by NKA, which are most probably mediated by a cross-talk between the NK(1) and NK(2) receptors.
authors: Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Campus Kiel, Hospitalstrasse 4, 24105 Kiel, Germany. utauer@gmx.de
authors: Ulrike
authors: U
authors: Tauer
authors: Yi
authors: Y
authors: Zhao
authors: Steven P
authors: SP
authors: Hunt
authors: Juraj
authors: J
authors: Culman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006120:Grooming / Q000187:drug effects; D007276:Injections, Intraventricular; D054833:Isoindoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015288:Neurokinin A / Q000494:pharmacology*; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D020239:Receptor Cross-Talk / Q000187:drug effects*; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000235:genetics*; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics*; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001549:Benzamides; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C054724:senktide; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A