title: Evidence for tachykinin NK-2 receptors in guinea-pig airways from binding and functional studies, using [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10).
abstract: The potent contractile responses of guinea-pig airways to neurokinin A (NKA) and neuropeptide gamma (NP gamma) are thought to be mediated by NK-2 receptors. However, NK-2 binding sites are not detectable using the radioligand [125I]-iodohistidyl-NKA. Here, a novel, highly selective iodinated radioligand, [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10), and a number of related peptides have been used to characterize NK-2 receptors on guinea-pig airways, using binding and functional studies. Specific binding of [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10), was saturable and to a single high affinity site, with KD 1.29 +/- 0.36 nM (n = 4). The rank order of potency for tachykinins and analogues as competitors for the binding was: [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) > or = NP gamma > or = [Lys5,MeLeu9,Nle10]-NKA(4-10) > NKA > or = SR 48968 >> MDL 29913 > or = substance P (SP) = [127I]-Bolton-Hunter NKA (BHNKA) > or = MEN 10207 > neurokinin B (NKB). Septide, [DPro9,Pro10,Trp11]-SP, the NK-1 selective ligands [Sar9,Met(O2)11]-SP, [Pro9]-SP and CP 96345, the NK-3 selective senktide, and calcitonin gene-related peptide (CGRP) were weak or ineffective. On guinea-pig isolated bronchi, the potency order of contractile agonists was: [Lys5,MeLeu9,Nle10]-NKA(4-10) > NKA > or = NP gamma > or = [Lys5,Tyr7,MeLeu9, Nle10]-NKA(4-10) > or = septide = BHNKA > or = [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) > or = [Sar9,Met(O2)11]-SP > or = NKB = [Pro9]-SP > or = SP >> senktide.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
authors.forename: X P
authors.initials: XP
authors.lastname: Zeng
authors.forename: S
authors.initials: S
authors.lastname: Lavielle
authors.forename: E
authors.initials: E
authors.lastname: Burcher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology
chemical_list: D009479:Neuropeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C080627:neurokinin A (4-10), Lys(5)-Tyr(I2)(7)-MeLeu(9)-Nle(10)-; D013373:Substance P; C054725:septide; D015288:Neurokinin A; D011761:Pyrrolidonecarboxylic Acid