title: [3H][beta-Ala8]neurokinin A-(4-10): a novel, selective radioligand for the tachykinin NK2 receptor.
abstract: The binding characteristics of the novel radioligand [3H][beta-Ala8]neurokinin A-(4-10) were assessed in hamster urinary bladder membranes. This labelled compound bound in a reversible, highly specific and concentration-dependent manner to a single class of high affinity binding sites with a Kd of 1.8 +/- 0.2 nM and a Bmax of 139 +/- 21 fmol/mg of protein. Specific binding of [3H][beta-Ala8]neurokinin A-(4-10) was displaced only by NK2, but not by NK1 or NK3, tachykinin receptor agonists and antagonists. Neurokinin A, [beta-Ala8]neurokinin A-(4-10), L 659877 [cyclo(Leu-Met-Gln-Trp-Phe-Gly)], MEN 10376 (H-Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Lys-NH2), MEN 10627 [cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2 beta-5 beta)] and SR 48968 [(S)-N-methyl-N-[4-(4-acetylamino-4-phenylpiperidino)-2- (3,4-dichlorophenyl)butyl]benzamide] displaced the binding with Ki values of 0.4 +/- 0.1 nM, 1.9 +/- 0.36 nM, 3.05 +/- 0.1 nM, 7.9 +/- 0.4 microM, 0.36 +/- 0.02 nM and 2.5 +/- 0.9 nM, respectively. Functional data, obtained in isolated hamster urinary bladder strips with the newly developed tachykinin NK2 receptor antagonists (MEN 10627 and SR 48968), showed a good agreement with binding data. This novel radioligand could represent a new useful tool for the assessment of tachykinin NK2 receptor antagonists.
authors.affiliation: Department of Pharmacology, Menarini Ricerche Sud, Pomezia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Goso
authors.forename: M
authors.initials: M
authors.lastname: Astolfi
authors.forename: M
authors.initials: M
authors.lastname: Parlani
authors.forename: S
authors.initials: S
authors.lastname: Manzini
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D006224:Cricetinae; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008647:Mesocricetus; D009119:Muscle Contraction / Q000187:drug effects; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D018042:Receptors, Neurokinin-3 / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
chemical_list: D001549:Benzamides; D008024:Ligands; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C064218:neurokinin A (4-10), beta-Ala(8)-; C090951:MEN 10627; C073839:SR 48968; D015288:Neurokinin A