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Titolo:
Binding and functional potency of neurokinin A analogues in the rat fundus: A structure-activity study
Autore:
Matuszek, MA; Comis, A; Burcher, E;
Indirizzi:
Univ New S Wales, Sch Physiol & Pharmacol, Sydney, NSW 2052, Australia Univ New S Wales Sydney NSW Australia 2052 l, Sydney, NSW 2052, Australia
Titolo Testata:
PHARMACOLOGY
fascicolo: 5, volume: 58, anno: 1999,
pagine: 227 - 235
SICI:
0031-7012(199905)58:5<227:BAFPON>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUBSTANCE-P; AUTORADIOGRAPHIC LOCALIZATION; TACHYKININ RECEPTORS; SELECTIVE AGONISTS; SMOOTH MUSCLES; RADIOLIGAND; ANTAGONIST; SITES;
Keywords:
neurokinin A; radioligand binding; structure activity; tachykinin NK-2 receptor; rat fundus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Burcher, E Univ New S Wales, Sch Physiol & Pharmacol, Sydney, NSW 2052, Australia Univ New S Wales Sydney NSW Australia 2052 NSW 2052, Australia
Citazione:
M.A. Matuszek et al., "Binding and functional potency of neurokinin A analogues in the rat fundus: A structure-activity study", PHARMACOL, 58(5), 1999, pp. 227-235

Abstract

Structure-activity relationships of neurokinin A (NKA) and the two analogues NKA(4-10) and [Nle(10)]NKA(4-10) were investigated at the rat fundus NK-2 receptor, using selected amino acid substitutions. Both radioligand binding with [I-125][Lys(5),Tyr(I-2)(7),MeLeu(9), Nle(10)] NKA(4-10) and functional studies were performed and correlated. In membrane binding experiments loss of His(1) and Lys(2), or replacement of Lys2 with Ala did not substantially alter binding affinity of NKA. NKA(4-10) free acid was unable to compete with the radioligand. [Nle(10)]NKA(4-10) binding affinity to rat fundusmembrane preparations was decreased when substituting Asp(4) with Gin or Asn, or Val(7) with either Tyr or lie. Replacement of Ser(5) with the negatively charged Glu also decreased the binding affinity, but substitution withthe positively charged Lys substantially increased the affinity of [Nle(10)] NKA(4-10) for the NK-2 receptor. Lengthening NKA(4-10) or [Nel(10)]NKA(4-10) with Ala(11) or Nle(11), respectively, decreased the binding affinity of the peptide. In both binding and functional studies, replacement of any of the residues of NKA(4-10), except for Ser(5), with alanine decreased theaffinity of the peptide for the NK-2 receptor. Ala substitutions at positions 4, 6, and very obviously at 8, 9 and 10 of NKA(4-10) yielded peptides unable to achieve a maximum contractile response, although they did not demonstrate antagonist activity. These data confirm the importance of the NKA carboxyl terminus, and the requirement for Phe(6), Val(7), Gly(8), Leu(9) and Met(10) integrity for interaction with the NK-2 receptor. They also suggest that Sers is a good site to target modifications leading to the design of new potential drugs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 03:25:07