General Aspects and History

After its first description in 1931 by Euler and Gaddum, substance P (P was the laboratory code for "peparation") remained the only mammalian member of the family of tachykinins for several decades. Tachykinins were defined as peptides sharing the common carboxy-terminal amino acid sequence Gly-Leu-Met-NH2 (Table 4.7).

In the 1970s, Chang and coworkers (1971) isolated and sequenced substance P. The family of mammalian tachykinins has subsequently grown with the isolation of four additional members. These peptides were named neurokinin A (NKA, neuromedin L or substance K), neuropeptide K (NPK), neurokinin B (NKB or neuromedin K). NKA is also present in two elongated forms, neuropeptide K and neuropeptide y (NPy).

In addition, some further tachykinins have been isolated from non-mammalian species (Table 4.7). These tachykinins include eledoisin, physalaemin and kassinin. The non-mammalian tachykinins will not be discribed here.

In parallel with the identification of the tachykinin family, several classes of tachykinin receptors were discovered. The receptors described to date are: tachy-

Table 4.7 Summary of mammalian and non-mammalian tachykinins. All these substances have a common N-terminal sequence (Gly-Leu-Met-NH2; indicated in italics).

Name

Sequence

Mammalian tachykinins Neuromedin K (NMK) or neurokinin B (NKB)

Neuropeptide K (NPK)

Neuropeptide y (NPy)

Substance K (SK) or neurokinin A (NKA) Substance P

Non-mammalian tachykinins

Eledoisin

Kassinin

Physalaemin

Asp-Met-His-Asp-Phe-Phe-Val-Gly-Leu-Met-NH2

Asp-Ala-Asp-Ser-Ser-Ile-Glu-Lys-Gln-Val-Ala-Leu-

Leu-Lys-Ala-Leu-Tyr-Gly-His-Gly-Gln-Ile-Ser-His-

Lys-Arg-His-Lys-Thr-Asp-Ser-Gly-Leu-Met-NH2

Asp-Ala-Gly-His-Gly-Gln-Ile-Ser-His-Lys-Arg-His-

Lys-Thr-Asp-Ser-Gly-Leu-Met-NH2

His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2

Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2

<Glu-Pro-Ser-Lys-Asp-Ala-Phe-Ile-Gly-Leu-Met-NH2

Asp-Val-Pro-Lys-Ser-Asp-Gln-Phe-Val-Gly-Leu-Met-

<Glu-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-Gly-Leu-Met-NH2

kinin NK1, NK2 and NK3 receptors. The endogeous agonists for the receptors are: substance P for NK1, NKA for NK2 and NKB for NK3.

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