NEUROKININ RECEPTOR SUBTYPES CHARACTERIZED BY BIOLOGICAL ASSAYS

Neurokinin receptors have been characterized by biological assays usin g naturally occurring and selective agonists as well as peptide and no n peptide antagonists. Six preparations have been used: the rabbit ven a cava and the rat urinary bladder, treated with a NK-2 receptor antag onist for the NK-1 receptor, the rabbit pulmonary artery and the hamst er urinary bladder for the NK-2, the sat portal vein and the guinea pi g ileum, treated with a NK-1 receptor antagonist, for the NK-3. Treatm ent with antagonists was required because of the presence (in some pre parations) of two functional sites contributing to the biological effe ct. Differences in the order of potency of agonists between each coupl e of receptors have been demonstrated, especially with tachykinins and the selective agonists. Such differences are even more evident with a ntagonists, some of which show apparent affinity (pA(2),) values 1.5 t o 3 log units higher in one than in the other member of each couple. B ased on data obtained in pharmacological experiments, it is concluded that NK-1, NK-2 and NK-3 receptors show differences strong enough to j ustify the assumption that their coding and/or expression diverge amon g species.