Neurokinin receptor subtypes characterized by biological assays

Abstract

Neurokinin receptors have been characterized by biological assays using naturally occurring and selective agonists as well as peptide and non peptide antagonists. Six preparations have been used: the rabbit vena cava and the rat urinary bladder, treated with a NK-2 receptor antagonist for the NK-1 receptor, the rabbit pulmonary artery and the hamster urinary bladder for the NK-2, the rat portal vein and the guinea pig ileum, treated with a NK-1 receptor antagonist, for the NK-3. Treatment with antagonists was required because of the presence (in some preparations) of two functional sites contributing to the biological effect. Differences in the order of potency of agonists between each couple of receptors have been demonstrated, especially with tachykinins and the selective agonists. Such differences are even more evident with antagonists, some of which show apparent affinity (pA2) values 1.5 to 3 log units higher in one than in the other member of each couple. Based on data obtained in pharmacological experiments, it is concluded that NK-1, NK-2 and NK-3 receptors show differences strong enough to justify the assumption that their coding and/or expression diverge among species.