Pharmacological characterization of novel mammalian tachykinins, neurokinin alpha and neurokinin beta

Abstract

Pharmacological studies were performed with neurokinin alpha and beta, new tachykinins isolated from porcine spinal cord, on smooth muscle preparations exhibiting two subtypes of substance P receptor (SP-P and SP-E receptors). The results showed that both neurokinin alpha and beta possessed the typical tachykinin activities and they exhibited SP-E-type ligand characteristics. The potency studies of SP6-11 and (Val8)SP6-11 have revealed that (VAL8)SP6-11 was comparable to SP6-11 in contracting the guinea-pig ileum (SP-P system), but greater than SP6-11 and also substance P in potentiating nerve stimulation-induced contraction of the rat vas deferens (SP-E system). The contractile response of the rat duodenum to neurokinin alpha was slow at onset and long-lasting compared with those to neurokinin beta and substance P. The residual immunoreactivity of each tachykinin in the organ bath decreased in parallel with the fading of the contractile response. The order of the half-life of each immunoreactive peptide was as follows: neurokinin alpha greater than neurokinin beta greater than substance P. The results were discussed from the viewpoints of structural significance in manifestation of pharmacological properties and in inactivation process, as well as the physiological roles of these novel mammalian tachykinins.