ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: (2-[125I]iodohistidyl1)Neurokinin A ([125I]NKA), which labels “septide-sensitive” but not classic NK1 binding sites in peripheral tissues, was used to determine whether septide-sensitive binding sites are also present in the rat brain. Binding studies were performed in the presence of SR 48968 (NK2 antagonist) and senktide (NK3 agonist) because [125I]NKA also labels peripheral NK2 binding sites and, as shown in this study, central NK3 binding sites. [125I]NKA was found to label not only septide-sensitive binding sites but also a new subtype of NK1 binding site distinct from classic NK1 binding sites. Both subtypes of [125I]NKA binding sites were sensitive to tachykinin NK1 antagonists and agonists but also to the endogenous tachykinins NKA, neuropeptide K (NPK), and neuropeptide γ (NPγ). However, compounds of the septide family such as substance P(6-11) [SP(6-11)] and propionyl-[Met(O2)11]SP(7-11) and some NK1 antagonists, GR 82334, RP 67580, and CP 96345, had a much lower affinity for the new NK1-sensitive sites than for the septide-sensitive sites. The hypothalamus and colliculi possess only this new subtype of NK1 site, whereas both types of [125I]NKA binding sites were found in the amygdala and some other brain structures. These results not only explain the central effects of septide or SP(6-11), but also those of NKA, NPK, and NPγ, which can be selectively blocked by NK1 receptor antagonists.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0751015.x
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