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Vol. 54, Issue 2, 285-322, June 2002

The Tachykinin Peptide Family

Cinzia Severini, Giovanna Improta, Giuliana Falconieri-Erspamer, Severo Salvadori and Vittorio Erspamer

Consiglio Nazionale delle Ricerche-Institute of Neurobiology and Molecular Medicine, Rome, Italy (C.S.); Department of Human Physiology and Pharmacology "Vittorio Erspamer", University "La Sapienza", Rome, Italy (G.I., G.F.-E., V.E.); and Department of Pharmaceutical Sciences, Università degli Studi, Ferrara, Italy (S.S.)

I. Introduction
II. Occurrence and Species Distribution of Tachykinin-Like Peptides
    A. Invertebrate Tachykinin-Like Peptides
    B. Prevertebrate Tachykinin-Like Peptides
        1. Amphioxus lanceolatus.
        2. Tunicata (Protocordata).
    C. Submammalian Vertebrate Tachykinins
        1. Amphibian Skin Tachykinins.
        2. Brain and Gut Tachykinins.
    D. Mammalian Tachykinins
        1. Mammalian Tachykinins and Their Biosynthesis.
III. Localization of Tachykinin-Like Peptides
    A. Non-Neuronal Localization
        1. Amphibian Skin.
        2. Invertebrate Salivary Glands.
        3. Normal Mammalian Tissues.
    B. Neuronal Localization
IV. Relationships between Structure/Activity Receptor Selectivity
    A. Residue Occupying Position 7 from the C Terminus
    B. Residue Occupying Position 4 from the C Terminus
    C. Residue Occupying Position 6 from the C Terminus
    D. Amino Acid Substitutions in the C-Terminal Tripeptide
    E. Pro Residue in the N-Terminal Sequence
V. Tachykinin-Like Peptides: Pharmacological Actions
    A. Cardiovascular System
        1. Systemic Arterial Blood Pressure
        2. Regional Circulation.
    B. Gastrointestinal Tract
        1. Motility.
        a. In Vitro Experiments.
        b. In Vivo Experiments.
        2. Secretions.
    C. Airways System
    D. Urogenital Tract
    E. Immune System
    F. Central Nervous System
        Action on discrete selected brain areas.
    G. Pain
    H. Neurogenic Inflammation
    I. Miscellaneous Pharmacological Actions
        1. Lachrymal Secretion.
        2. Histamine Release.
VI. Tachykinins in Human Diseases and Therapeutics
    A. Tachykinin Receptor Agonists
    B. Tachykinin Receptor Antagonists
VII. General Conclusions
References

The tachykinin peptide family certainly represents one of the largest peptide families described in the animal organism. So far, more than 40 tachykinins have been isolated from invertebrate (insects, worms, and molluscs), protochordate, and vertebrate (skin, gastrointestinal tract, peripheral and central nervous system) tissues. Substance P (SP), first identified by bioassay as early as 1931 but sequenced only in 1971, several years after the elucidation of the structure of eledoisin from molluscan tissues and of physalaemin from amphibian skin, may be considered as a prototype of the tachykinins. Hitherto, as many as 19 tachykinins have been isolated from amphibian integument, and eight additional peptides have been isolated from amphibian gut and brain. Counterparts of skin tachykinins in mammalian tissues are SP, neurokinin A, and neurokinin B. Three main receptor subtypes for the tachykinins have been identified (NK1, NK2, and NK3), but their number is probably destined to increase. It is obvious that the peripheral and central effects of the tachykinins may substantially vary depending on the activation of different receptor subtypes. Matters are further complicated by the frequent capacity of the single tachykinins to bind, although with different affinity, to more receptors. It has been recognized that tachykinins have a variety of effects in physiological and pathological conditions, and there is evidence suggesting intrinsic neuroprotective and neurodegenerative properties of these neuropeptides. This review provides an update on the current body of knowledge regarding tachykinin occurrence and distribution in the animal kingdom, from the lowest invertebrates to man, and the physiological and pharmacological actions of tachykinins outlining the pregnant importance of this large peptide family.

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This is the last unfinished review written by professor Vittorio Erspamer before he died suddenly in October 1999. His collaborators are proud to present this review on his behalf and to honor his memory as an enthusiastic and intuitive researcher who enriched the knowledge of new and unimagined agents and actions all over the world.

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0031-6997/02/5402-0285$07.00/0
PHARMACOLOGICAL REVIEWS
Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics

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