Neurochinina A

Neurochinina A
Neurochinina A
Neurochinina A
Caratteristiche generali
Formula bruta o molecolareC50H80N14O14S
Massa molecolare (u)1133,32
Numero CAS86933-74-6
PubChem13561815
SMILES
CC(C)CC(C(=O)NC(CCSC)C(=O)N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C(CO)NC(=O)C(CC(=O)O)NC(=O)C(C(C)O)NC(=O)C(CCCCN)NC(=O)C(CC2=CN=CN2)N
Indicazioni di sicurezza
Frasi H---
Consigli P---[1]
Precursore 1 della tachichinina
Precursore della Tachichinina A
Gene
HUGOTAC1 TAC2, NKNA
Entrez6863
LocusChr. 7 q21-q22
Proteina
Numero CAS86933-74-6
OMIM162320
UniProtP20366

La Neurochinina A (un tempo nota come Sostanza K) è un neuropeptide, un polipeptide a catena corta, appartenente alla famiglia delle tachichinine, che agisce da neurotrasmettitore nei mammiferi[2].

Struttura

Il polipeptide è composto da 10 aminoacidi con sequenza: His-Lys-Thr-Asn-Ser-Phe-Val-Gly-Leu-Met[3].

La regione N-terminale non è essenziale per l'attività. Sono essenziali per l'attività invece i frammenti contenenti l'estremità C-terminale: Peptidi privi dei primi 4 amminoacidi hanno attività maggiore o uguale del peptide completo dei dieci aminoacidi[4].

Sintesi

La sintesi delle tachichinine si verifica soprattutto dai neuroni e i peptidi sono liberati dagli assoni. Di recente è stata dimostrata produzione di neuropeptidi anche da cellule extraneuronali, come granulociti eosinofili, macrofagi, linfociti. La produzione della Neurochinina A, come pure della Sostanza P, del Neuropeptide K e del Neuropeptide Y, è regolata dal gene preprotachichinina-I (PPT-I o PPT-A) che, per motivi storici, è chiamato negli uomini TAC1 e TAC3, ed è equivalente al gene Tac1 del topo[5]. Le preprotachichinine sono poi tagliate in polipeptidi più piccoli.

Recettore

Il recettore endogeno della Sostanza P è il recettore 1 della neurochinina (NK1R), appartenente alla famiglia dei recettori accoppiati a proteine G[6],[7].

Meccanismo d'azione

La Neurochinina A svolge diverse funzioni nell'organismo animale. Come tutte le tachichinine, la Neurochinina A è in grado di eccitare neuroni[8], dilatare i vasi sanguigni[9] e far contrarre la muscolatura liscia per esempio quella della parete vescicale, uterina o delle vie aeree[10], ed è uno dei principali mediatori della peristalsi intestinale[11]. Non sono invece ben noti gli effetti sul sistema immunitario,[12].

L'estremità attiva N-terminale del Neuropeptide K (che è stato chiamato anche Neurochinina K[13]) e del Neuropeptide gamma è più lunga di quella della Neurochinina A, sebbene tutti siano stati prodotti per mezzo dello stesso splicing alternativo del medesimo gene[14].

Note

  1. ^ Sigma Aldrich; rev. del 01.12.2011
  2. ^ Vittorio Erspamer: "Sostanze Bioattive: dalla pelle di un anfibio al cervello di uomo", Prolusione tenuta nell'inaugurazione del 205º Anno Accademico dell'Accademia dei XL, Marzo 1987 Copia archiviata, su accademiaxl.it. URL consultato il 25 novembre 2007 (archiviato dall'url originale il 19 ottobre 2007).
  3. ^ Helke CJ, Krause JE, Mantyh PW, Couture R, Bannon MJ, Diversity in mammalian tachykinin peptidergic neurons: multiple peptides, receptors, and regulatory mechanisms, in FASEB J, vol. 4, n. 6, 1990 Apr 1, pp. 1606-15, PMID 1969374.
  4. ^ Clapéron A, Rose C, Gane P, Collec E, Bertrand O, Ouimet, The Kell protein of the common K2 phenotype is a catalytically active metalloprotease, whereas the rare Kell K1 antigen is inactive. Identification of novel substrates for the Kell protein, in J Biol Chem, vol. 280, n. 22, 2005 Jun 3, pp. 21272-83, PMID 15769748.
  5. ^ Carter MS, Krause JE, Structure, expression, and some regulatory mechanisms of the rat preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K, and neuropeptide gamma, in J Neurosci, vol. 10, n. 7, 1990, pp. 2203-14, PMID 1695945.
  6. ^ Maggi C, Patacchini R, Rovero P, Giachetti A, Tachykinin receptors and tachykinin receptor antagonists, in J Auton Pharmacol, vol. 13, n. 1, 1993, pp. 23-93, PMID 8382703.
  7. ^ Regoli D, Boudon A, Fauchére J, Receptors and antagonists for substance P and related peptides, in Pharmacol Rev, vol. 46, n. 4, 1994, pp. 551-99, PMID 7534932.
  8. ^ Chahl LA, Tachykinins and neuropsychiatric disorders, in Curr Drug Targets, vol. 7, n. 8, 2006 Aug, pp. 993-1003, PMID 16918327.
  9. ^ Walsh DA, F McWilliams D, Tachykinins and the cardiovascular system, in Curr Drug Targets, vol. 7, n. 8, 2006 Aug, pp. 1031-42, PMID 16918331.
  10. ^ Groneberg DA, Harrison S, Dinh QT, Geppetti P, Fischer A, Tachykinins in the respiratory tract, in Curr Drug Targets, vol. 7, n. 8, 2006 Aug, pp. 1005-10, PMID 16918328.
  11. ^ Lecci A, Capriati A, Altamura M, Maggi CA, Tachykinins and tachykinin receptors in the gut, with special reference to NK2 receptors in human, in Auton Neurosci, vol. 126-127, 2006 Jun 30, pp. 232-49, PMID 16616700.
  12. ^ Zhang Y, Berger A, Milne CD, Paige CJ, Tachykinins in the immune system, in Curr Drug Targets, vol. 7, n. 8, 2006 Aug, pp. 1011-20, PMID 16918329.
  13. ^ Dornan WA, Vink KL, Malen P, Short K, Struthers W, Barrett C. "Site-specific effects of intracerebral injections of three neurokinins (neurokinin A, neurokinin K, and neurokinin gamma) on the expression of male rat sexual behavior." Physiol Behav. 1993 Aug;54(2):249-58. PMID 7690487
  14. ^ Carter MS, Krause JE. "Structure, expression, and some regulatory mechanisms of the rat preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K, and neuropeptide gamma." J Neurosci. 1990 Jul;10(7):2203-14, PMID 1695945

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