Tachykinin peptides are one of the largest families of

neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

s, found from

amphibian Amphibians are tetrapod, four-limbed and ectothermic vertebrates of the Class (biology), class Amphibia. All living amphibians belong to the group Lissamphibia. They inhabit a wide variety of habitats, with most species living within terres ...

s to

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

s. They were so named due to their ability to rapidly induce contraction of gut tissue. The tachykinin family is characterized by a common

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

sequence, Phe-X-

Gly Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

- Leu- Met-NH2, where X is either an

Aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

or an

Aliphatic In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, or ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

. The

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s that produce tachykinins encode precursor proteins called

preprotachykinin Preprotachykinins are precursor proteins that are modified into tachykinin peptides. Via alternative splicing and post-translational modifications, preprotachykinins produce multiple peptide neurotransmitters. There are two human preprotachykini ...

s, which are chopped apart into smaller

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s by

posttranslational Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosomes ...

proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...

processing. The genes also code for multiple

splice form Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in ...

s that are made up of different sets of peptides. Tachykinins excite neurons, evoke behavioral responses, are potent

vasodilator Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...

s, and contract (directly or indirectly) many smooth muscles. Tachykinins are from ten to twelve residues long. The two human tachykinin genes are called

TAC1 Preprotachykinin-1, (abbreviated PPT-1, PPT-I, or PPT-A), is a precursor protein that in humans is encoded by the ''TAC1'' gene. Isoforms and derivatives The protein has four isoforms—alpha-, beta-, gamma-, and delta-PPT—which can variably u ...

and

TAC3 Tachykinin-3 is a protein that in humans is encoded by the ''TAC3'' gene. See also *Neurokinin B *Tachykinin receptor 3 Tachykinin receptor 3, also known as TACR3, is a protein which in humans is encoded by the ''TACR3'' gene. Function This ...

for historical reasons, and are equivalent to Tac1 and Tac2 of the mouse, respectively. TAC1 encodes

neurokinin A Neurokinin A (NKA), formerly known as Substance K, is a neurologically active peptide translated from the pre-protachykinin gene. Neurokinin A has many excitatory effects on mammalian nervous systems and is also influential on the mammalian inflam ...

(formerly known as substance K),

neuropeptide K Neuropeptide K (also known as neurokinin K), is a protein encoded by the TAC1 gene. It is an elongated derivative of the N-terminus of neurokinin A as the final post-translational processing product of beta-preprotachykinin. Like neurokinin A, ...

(which has also been called neurokinin K),

neuropeptide gamma Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

, and

Substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clos ...

. Alpha, beta, and gamma splice forms are produced; the alpha form lacks

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

6 and the gamma form lacks exon 4. All three splice forms of TAC1 produce substance P, but only the beta and gamma forms produce the other three peptides. Neuropeptide K and neuropeptide gamma are N-terminally longer versions of neurokinin A that appear to be final peptide products in some tissues. TAC3 encodes

neurokinin B Neurokinin B (NKB) belongs in the family of tachykinin peptides. Neurokinin B is implicated in a variety of human functions and pathways such as the secretion of gonadotropin-releasing hormone. Additionally, NKB is associated with pregnancy in fem ...

. The best known tachykinin is

Receptors

There are three known

mammalian Mammals () are a group of vertebrate animals constituting the class (biology), class Mammalia (), characterized by the presence of mammary glands which in Female#Mammalian female, females produce milk for feeding (nursing) their young, a ...

tachykinin Tachykinin peptides are one of the largest families of neuropeptides, found from amphibians to mammals. They were so named due to their ability to rapidly induce contraction of gut tissue. The tachykinin family is characterized by a common C-termi ...

receptors termed NK₁, NK₂ and NK₃. All are members of the

7 transmembrane G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

g protein-coupled G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

family of receptors and induce the activation of

phospholipase C Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role ...

, producing

inositol triphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the p ...

. NK₁, NK₂ and NK₃ selectively bind to

substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clos ...

, and

, respectively. Whilst the receptors are not specific to any individual tachykinin, they do have differing affinity for the tachykinins: * NK₁: SP > NKA > NKB * NK₂: NKA > NKB > SP * NK₃: NKB > NKA > SP Antagonists of neurokinin-1 (NK₁) receptors (

NK1 receptor antagonist Neurokinin 1 (NK1) antagonists (-pitants) are a novel class of medications that possesses unique antidepressant, anxiolytic, and antiemetic properties. NK-1 antagonists boost the efficacy of 5-HT3 antagonists to prevent nausea and vomiting. The dis ...

s), through which substance P acts, have been proposed to belong to a new class of

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

s, while NK₂ antagonists have been proposed as

anxiolytics An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

and NK₃ antagonists have been proposed as

antipsychotics Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...

. Tachykinin peptides are also involved in

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

, and tachykinin receptor antagonists have been researched for use in treating inflammatory conditions such as

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

and

irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...

. The main use for which these antagonist drugs have been applied so far, however, is as

antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may ...

s, in both human and veterinary medicine. Examples of tachykinin antagonists include: *

Aprepitant Aprepitant, sold under the brand name Emend among others, is a medication used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and de ...

Casopitant Casopitant (), former tentative trade names Rezonic (U.S.) and Zunrisa (Europe), is an NK1 receptor antagonist which was undergoing research for the treatment of chemotherapy-induced nausea and vomiting. It was under development by GlaxoSmithKli ...

Fosaprepitant Fosaprepitant (Emend for Injection (US), Ivemend (EU)) is an antiemetic medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent d ...

Maropitant Maropitant (INN; trade name: Cerenia ), used as maropitant citrate (USAN), is a neurokinin-1 (NK1) receptor antagonist developed by Zoetis specifically for the treatment of motion sickness and vomiting in dogs. It was approved by the FDA in 200 ...

Nepadutant Nepadutant (INN) (code name MEN-11420) is a glycosylated bicyclic cyclohexapeptide drug which acts as a highly selective NK2 receptor antagonist. It was developed by the Menarini Group and investigated for the treatment of functional gastroin ...

Osanetant Osanetant (developmental code name SR-142,801) is a Tachykinin receptor 3, neurokinin 3 receptor receptor antagonist, antagonist which was developed by Sanofi-Synthélabo and was being researched for the treatment of schizophrenia but was discont ...

Saredutant Saredutant (SR-48,968) is a drug that acts as a Tachykinin receptor 2, NK2 receptor receptor antagonist, antagonist. It was under development by Sanofi-Aventis as a novel antidepressant and anxiolytic and made it to Phase III clinical trials, pha ...

Talnetant Talnetant (SB-223,412) is a neurokinin 3 receptor antagonist developed by GlaxoSmithKline, which is being researched for several functions (primarily treatment of irritable bowel syndrome, despite a 2007 study finding no statistically significan ...

Receptors

Subfamilies

References

External links