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.