Effects of some neurokinin A analogues on tachykinin-induced contraction of guinea pig trachea.
A series of analogues of neurokinin A (NKA) has been synthesized and characterized by testing for their abilities, in vitro, to contract guinea pig tracheal smooth muscle or to antagonize NKA-, NKB- and SP-induced contraction of this tissue. Substitution of NKA residues Gly8 or Leu9 by conformationally restricting amino acids produced peptides that were antagonists of NKA action, but the type and specificity of the antagonism depended on the size of the peptide. Thus, while [Ala5, Aib8, Leu10]NKA(2-10) showed no agonism and was a specific, competitive antagonist of NKA, [Ala5, Aib8, Leu10]NKA(4-10) was a noncompetitive antagonist of NKA and substance P (SP) and was itself a weak agonist at concentrations above 10(-7) M.
Abu Shanab
A A
AA
Division of Biochemistry, School of Biology and Biochemistry, Queen's University of Belfast, N. Ireland, UK.
Allen
J M
JM
Guthrie
D J
DJ
Irvine
G B
GB
Murphy
R F
RF
Walker
B
B
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015320:Tachykinins / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D009842:Oligopeptides; D015320:Tachykinins; D015288:Neurokinin A; D002217:Carbachol