Tachykinin receptor 1

Source: Wikipedia, the free encyclopedia.
(Redirected from
Neurokinin 1 receptor
)
TACR1
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_015727
NM_001058

NM_009313

RefSeq (protein)

NP_001049
NP_056542

NP_033339

Location (UCSC)Chr 2: 75.05 – 75.2 MbChr 6: 82.38 – 82.54 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The tachykinin receptor 1 (TACR1) also known as neurokinin 1 receptor (NK1R) or substance P receptor (SPR) is a

tachykinins. The protein is the product of the TACR1 gene.[5]

Properties

Tachykinins are a family of

N-terminal region varies between different tachykinins.[6][7][8] The term tachykinin originates in the rapid onset of action caused by the peptides in smooth muscles.[8] Substance P (SP) is the most researched and potent member of the tachykinin family. It is an undecapeptide with the amino acid sequence Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2.[6] SP binds to all three of the tachykinin receptors, but it binds most strongly to the NK1 receptor.[7]

Tachykinin NK1 receptor

G-proteins.[9][10] The binding site for substance P and other agonists and antagonists is found between the second and third transmembrane domains. The NK-1 receptor is found on human chromosome 2 and is located on the cell's surface as a cytoplasmic receptor.[11]

Distribution and function

The NK1 receptor can be found in both the central and peripheral nervous system. It is present in neurons, brainstem, vascular endothelial cells, muscle, gastrointestinal tracts, genitourinary tract, pulmonary tissue, thyroid gland and different types of immune cells.[9][12][8][10] The binding of SP to the NK1 receptor has been associated with the transmission of stress signals and pain, the contraction of smooth muscles and inflammation.[13] NK1 receptor antagonists have also been studied in migraine, emesis and psychiatric disorders. In fact, aprepitant has been proved effective in a number of pathophysiological models of anxiety and depression.[14] Other diseases in which the NK1 receptor system is involved include asthma, rheumatoid arthritis and gastrointestinal disorders.[15]

Mechanism

SP is synthesized by neurons and transported to

synaptic vesicles; the release of SP is accomplished through the depolarizing action of calcium-dependent mechanisms.[6]
When NK1 receptors are stimulated, they can generate various
catecholamines and play a role in the regulation of blood pressure and hypertension. Likewise, SP is known to bind to N-methyl-D-aspartate (NMDA) receptors by eliciting excitation with calcium ion influx, which further releases nitric oxide. Studies in frogs have shown that SP elicits the release of prostaglandin E2 and prostacyclin by the arachidonic acid pathway, which leads to an increase in corticosteroid output.[8]

In combination therapy, NK1 receptor antagonists appear to offer better control of delayed emesis and post-operative emesis than drug therapy without NK1 receptor antagonists. NK1 receptor antagonists block responses to a broader range of emetic stimuli than the established 5-HT3 antagonist treatments.[15] It has been reported that centrally-acting NK1 receptors antagonists, such as CP-99994, inhibit emesis induced by apomorphine and loperimidine, which are two compounds that act through central mechanisms.[12]

Clinical significance

This receptor is considered an attractive

anti-depressants.[17][18] It is also a potential treatment for alcoholism and opioid addiction.[19] In addition, it has been identified as a candidate in the etiology of bipolar disorder.[20] Finally NK1R antagonists may also have a role as novel antiemetics[21] and hypnotics.[22][23]

Ligands

Many selective ligands for NK1 are now available, several of which have gone into clinical use as

antiemetics
.

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115353 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030043 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. PMID 1718267
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  11. . Retrieved 28 January 2023.
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Further reading

External links