Insight into Molecular and Functional Diversity of Tachykinins and their Receptors

Tachykinins (TKs) and their structurally related peptides constitute the largest peptide superfamily in the animal kingdom. TKs have been shown to play various physiological roles not only as major brain-gut peptides but also as endocrine-paracrine hormones in chordates and exocrine factors in amphibians. Recent studies have also revealed that the biological roles of TKs as brain-gut peptides and endocrine-paracrine factors are essentially conserved in protochordates, and that alternative splicing mechanism in mammalian TK genes were established during the evolution of vertebrates. Protostomes possess two structurally and functionally different peptides; invertebrate TKs (inv-TKs) serve as toxin-like compounds secreted from the salivary gland of several organisms, whereas TK-related peptides (TKRPs) are functional counterparts for chordate TKs. Additionally, a TKRP-like sequence was detected in a diploblastic organism. The dramatic difference in structural organizations between TKRP precursors and chordate TK precursors clearly indicates the distinct evolutionary processes of TKs and TKRPs. Despite high sequence homology, TK receptors manifest selective affinity to their endogenous ligands, while TKRPs exhibit redundant activity at their receptors. Moreover, in addition to nociceptive, inflammatory, and contractile effects as brain-gut peptides, a number of studies have revealed novel biological effects of TKs on the hypothalamus and genital organs, revealing the biological roles of TKs as pivotal regulators of reproduction. These findings shed light on complicated evolutionary lineages of both structures and functions of the TK-TKRP superfamily and their receptors. In this review, we present basic and latest knowledge of the TK-TKRP superfamily with various points of view.