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Tachykinin NK(2) receptor mediates contraction and ion transport in rat colon by different mechanisms.

Abstract：

:We have characterized the tachykinin NK(2) receptor-mediated contraction and vectorial ion transport responses in the muscularis mucosae and mucosa of the rat isolated distal colon, respectively. The tachykinin NK(2) receptor-selective antagonist nepadutant (c([(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2beta-5beta))) produced competitive antagonism of [betaAla(8)]neurokinin A-(4-10)-induced contraction (pK(B) = 9.3) in the muscularis mucosae, and insurmountable blockade of increases in short-circuit current (I(sc)) responses (pK(B) = 8.6) in the mucosa. However, this latter effect was completely reversed by washout of the antagonist. [betaAla(8)]Neurokinin A-(4-10)-induced contractions were unaffected by indomethacin (3 microM). In sharp contrast, I(sc) responses induced by [betaAla(8)]neurokinin A-(4-10) (100 nM) were inhibited (>70%) by indomethacin (3 microM), while I(sc) responses to substance P (3 microM) were unchanged. Our study provides the first evidence that in the same organ stimulation of tachykinin NK(2) receptors leads to two independent responses mediated by different effector mechanisms both of which are blocked (albeit with different kinetics) by the potent and selective tachykinin NK(2) receptor antagonist, nepadutant.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Patacchini R,Cox HM,Ståhl S,Tough IR,Maggi CA

doi

10.1016/s0014-2999(01)00836-6

keywords:

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

277-83

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

S0014299901008366

journal_volume

415

pub_type

杂志文章

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