title: Characterization of neurokinin binding sites in rat brain membranes using highly selective ligands.
abstract: Neurokinin binding sites are distributed throughout the central and peripheral nervous system and three neurokinin binding sites have been described until now. The endogenous tachykinins substance P, neurokinin A and eledoisin as well as the highly selective neurokinin ligands [Arg6, Sar9, Met(O2)11]SP6-11 and [Sar9, Met(O2)11]SP (for neurokinin-1), MEN 10,376 and [beta Ala8]NKA(4-10) (for neurokinin-2) and senktide and [MePhe7]NKB (for neurokinin-3) were used for displacement experiments. Neurokinin-1 and -3 binding sites were demonstrated in membrane preparations of rat striatum, frontal cortex, hypothalamus, hippocampus and amygdala by displacing [125I]-BH-substance P and [125I]-BH-eledoisin, respectively. The highly selective neurokinin-2 ligand MEN 10,376 was iodinated to measure neurokinin-2 binding sites, but no specific binding was found in membranes of all brain regions, the spinal cord, the stomach, the urinary bladder or the guinea-pig lung, probably due to loss of binding properties. We conclude that neurokinin-1 and neurokinin-3 binding sites are distributed in several brain regions of the rat brain and selective neurokinin ligands are important tools to characterize neurokinin binding sites.
authors.affiliation: Department of Psychiatry, University Hospital Innsbruck, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Humpel
authors.forename: A
authors.initials: A
authors.lastname: Saria
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001923:Brain Chemistry; D004600:Eledoisin / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000145:classification / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism; D015320:Tachykinins
chemical_list: D008024:Ligands; D008565:Membrane Proteins; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C054724:senktide; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D013373:Substance P; D004600:Eledoisin; D015288:Neurokinin A