Tachykinin Receptors: Binding and Cellular Activity Assays

Abstract

This chapter discusses the technical aspects of the methods related to treatment of tachykinin (TK) receptors. TKs represent a family of structurally related peptides that share a common C-terminal amino acid sequence, exhibit different rank order of potency according to the tissue investigated, and show some analogy in their biological effects. Mammalian TK are derived from large precursors encoded by two genes, namely, the preprotachykinins A (PPTA) and preprotachykinins B (PPTB) genes. The PPTA large precursors generate substance P (SP) alone or both SP and neurokinin A (NKA), SP and neuropeptide K (NPK), or SP and NPγ through alternative splicing, whereas the PPTB precursors give rise to neurokinin B (NKB) alone. NK1 receptors are characterized by their preferential affinity for SP. NK2 receptors are characterized by their preferential affinity for NKA. NK3 receptors are characterized by their preferential affinity for NKB. Binding studies have demonstrated that TK analogs recognize TK receptors, but the agonist or antagonist properties of these compounds have been demonstrated using biological assays on peripheral isolated organs. It is reported that dog carotid artery, rabbit pulmonary artery, and rat portal vein distinguish responses are mediated by NK1, NK2, and NK3 receptors. However, there is not always a perfect correlation between the relative potencies of TK or analogs in binding studies and those in assays made on these peripheral organs.