Parallel bioassay of 39 tachykinins on 11 smooth muscle preparations. Structure and receptor selectivity/affinity relationship.
Parallel bioassay on smooth muscle preparations demonstrated that: all TKs having a neutral or basic residue at position 7 from the C-terminus show a clear-cut preference for the NK1 TK receptor, reinforced by the presence of the aromatic doublet Phe-Phe or Phe-Tyr (aromatic TKs); all aliphatic TKs (Phe-Ile/Val) having an acidic residue at position 7 show a clear-cut preference for NK2/NK3 receptors, generally without selectivity for a single receptor. However, in aromatic TKs having the same acidic residue, the preference for NK2/NK3 receptors is weakened, with a more or less pronounced co-preference for the NK1 receptor. Amino acid substitutions in the C-terminal tripeptide may influence receptor affinity.
Severini
C
C
CNR - Institute of Neurobiology, Viale C. Marx 15, I-00137, Rome, Italy. tindaro.renda@uniroma.it
Salvadori
S
S
Guerrini
R
R
Falconieri-Erspamer
G
G
Mignogna
G
G
Erspamer
V
V
D000818:Animals; D001681:Biological Assay; D006168:Guinea Pigs; D007532:Isoleucine; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010649:Phenylalanine / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000378:metabolism; D015320:Tachykinins / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D014443:Tyrosine / Q000737:chemistry
D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; D015320:Tachykinins; D007532:Isoleucine; D014443:Tyrosine; D010649:Phenylalanine; D011392:Proline