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 anal ogues substituted in position 7 were tested in bioassays for tachykini n NK1, NK2 and NK3 receptors. Scyliorhinin I behaved as a full agonist at tachykinin NK1 receptors of the guinea-pig ileum longitudinal musc le and at NK2 receptors of the rabbit pulmonary artery and hamster tra chea. In these three preparations scyliorhinin I was as potent agonist as substance P methylester and neurokinin A, respectively. Evidence f or activation of tachykinin NK1 and NK2 receptors by scyliorhinin I wa s obtained by using the selective tachykinin antagonists FK 888, MEN 1 0,376 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 [Ile 7]scyliorhinin I were 3-25 times weaker than scyliorhinin I itself at NK1 and NK2 receptors. [Phe7]scyliorhinin I, [Phe(F)7]scyliorhinin I a nd [Phe(Cl)7]scyliorhinin I were as potent as scyliorhinin I at NK1 re ceptors in the guinea-pig ileum, while they showed 10-30 times lower a ffinity 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.