Effect of scyliorhinin I and synthetic scyliorhinin I derivatives at mammalian tachykinin NK1, NK2 and NK3 receptors.
The dogfish tachykinin peptide scyliorhinin I and a number of its analogues substituted in position 7 were tested in bioassays for tachykinin NK1, NK2 and NK3 receptors. Scyliorhinin I behaved as a full agonist at tachykinin NK1 receptors of the guinea-pig ileum longitudinal muscle and at NK2 receptors of the rabbit pulmonary artery and hamster trachea. In these three preparations scyliorhinin I was as potent agonist as substance P methylester and neurokinin A, respectively. Evidence for activation of tachykinin NK1 and NK2 receptors by scyliorhinin I was obtained by using the selective tachykinin antagonists FK 888, MEN 10,376 and L 659,877. Scyliorhinin I was poorly active as an agonist at NK3 receptors of the rat portal vein. Among scyliorhinin I analogues, [beta-(2-naphthyl)-Ala7]scyliorhinin I, [Val7]scyliorhinin I and [Ile7]scyliorhinin I were 3-25 times weaker than scyliorhinin I itself at NK1 and NK2 receptors. [Phe7]scyliorhinin I, [Phe(F)7]scyliorhinin I and [Phe(Cl)7]scyliorhinin I were as potent as scyliorhinin I at NK1 receptors in the guinea-pig ileum, while they showed 10-30 times lower affinity than scyliorhinin I for NK2 receptors. The present results are discussed in relation to the importance of position 7 in determining the potency and selectivity of scyliorhinin I analogues at tachykinin receptors.
Patacchini
R
R
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Quartara
L
L
Rolka
K
K
Zboinska
J
J
Kupryszewski
G
G
Maggi
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D004151:Dipeptides / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013373:Substance P / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D004151:Dipeptides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; C048918:scyliorhinin I; C073361:cyclo(Gln-Trp-Phe-Gly-Leu-Met); C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; C078949:FK 888; D013373:Substance P; D015288:Neurokinin A