Further evidence for the presence of "septide-sensitive" tachykinin binding sites in tissues possessing solely NK(1) tachykinin receptors.
Binding experiments performed with [(125)I]-NKA allowed us to demonstrate the presence of "septide-sensitive" specific binding sites on membranes from rat CHO cells transfected with the NK(1) receptor cDNA (CHO-rat-NK1 cells), human astrocytoma U373 MG, or mouse cortical astrocytes, cells which express NK(1) but neither NK(2) nor NK(3) receptors. In all cases, [(125)I]-NKA was specifically bound with high affinity (2 to 5 nM) to a single population of sites. In the three preparations, pharmacological characteristics of [(125)I]-NKA binding sites were notably different from those of classical NK(1) binding sites selectively labelled with [(125)I]-BHSP. Indeed, the endogenous tachykinins NKA, NPK, and NKB and the septide-like compounds such as septide, SP(6-11), ALIE-124, [Apa(9-10)]SP, or [Lys(5)]NKA(4-10) had a much higher affinity for [(125)I]-NKA than [(125)I]-BHSP binding sites. Interestingly, differences were also found in the ratio of B(max) values for [(125)I]-NKA and [(125)I]-BHSP specific bindings from one tissue to another. These latter observations suggest that these two types of NK(1) binding sites are present on distinct NK(1) receptor isoforms (or conformers). Finally, while several tachykinins and tachykinin-related compounds stimulated cAMP formation or increased inositol phosphate accumulation in CHO-rat-NK1 cells, these compounds only increased the accumulation of inositol phosphates in the two other preparations.
Torrens
Y
Y
Chaire de Neuropharmacologie, INSERM U114, Collège de France, 11 Place Marcelin-Berthelot, Paris Cedex 05, 75231, France.
Beaujouan
J C
JC
Saffroy
M
M
Glowinski
J
J
D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007457:Iodine Radioisotopes; D054833:Isoindoles; D051379:Mice; D015288:Neurokinin A / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011869:Radioligand Assay; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives* / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007211:Indoles; D007457:Iodine Radioisotopes; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D020033:Protein Isoforms; D018040:Receptors, Neurokinin-1; D013777:Tetrazoles; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; C054725:septide; D015288:Neurokinin A; C103207:vofopitant; D011761:Pyrrolidonecarboxylic Acid