Receptor-mediated specific biological activity of a beta-amyloid protein fragment for NK-1 substance P receptors.
A beta-amyloid protein fragment AP21-35 (tetradeapeptide with amino acid residues 21-35) was found to be a highly selective agonist of substance P receptors (NK-1) among three tachykinin receptor subtypes. This peptide fragment contracted the smooth muscle preparations of guinea pig ileum in a dose dependent manner (EC50 = 22 microM). This activity was completely reversed by CP-96,345-1, a specific antagonist of NK-1 receptors, whereas atropine for NK-3 had no effect. The peptide was inactive in rat vas deferens which contains predominantly NK-2 receptors. These results indicated that AP21-35 is a highly selective agonist for NK-1 receptors. In the radio-ligand receptor binding assay using [125I]-Bolton-Hunter substance P to membranes from guinea pig ileum, the fragment exhibited a distinct dose-response curve (IC50 = 11 microM). All the present data strongly suggest that beta-amyloid protein function as a peptide ligand of substance P receptors with some pathophysiologic activities.
Shimohigashi
Y
Y
Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka, Japan.
Matsumoto
H
H
Takano
Y
Y
Saito
R
R
Iwata
T
T
Kamiya
H
H
Ohno
M
M
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D001713:Biphenyl Compounds; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C081625:amyloid beta-protein (21-35); D013373:Substance P; D015288:Neurokinin A; C066892:CP 96345