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Autoinhibitory function of the sympathetic prejunctional neuropeptide Y Y(2) receptor evidenced by BIIE0246.

Abstract：

:The significance of neuropeptide Y Y(2) receptors in sympathetic nonadrenergic transmission was investigated using the novel selective antagonist BIIE0246 ((S)-N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cyclopentyl]acetyl]-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamide). In anaesthetized pigs pretreated with reserpine, and after transection of sympathetic nerves (depleted of noradrenaline), electrical stimulation of renal and splanchnic sympathetic nerves evoked vasoconstriction in, and overflow of neuropeptide Y-like immunoreactivity from, kidney and spleen, respectively. In the presence of BIIE0246, the nerve-evoked overflows of neuropeptide Y-like immunoreactivity were markedly increased and the splenic vasoconstrictor response prolonged. In addition, BIIE0246 caused splenic vasodilatation per se in this model where basal levels of circulating neuropeptide Y exceed 40 pM. It is concluded that endogenous neurogenical neuropeptide Y regulates its own release via activation of sympathetic prejunctional inhibitory neuropeptide Y Y(2) receptors in both spleen and kidney in the reserpinized pig. Moreover, when circulating levels of neuropeptide Y are moderately increased, activation of neuropeptide Y Y(2) receptors seems to contribute to basal splenic vascular tone.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Malmström RE,Lundberg JO,Weitzberg E

doi

10.1016/s0014-2999(02)01371-7

keywords:

subject

Has Abstract

pub_date

2002-03-29 00:00:00

pages

113-9

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014299902013717

journal_volume

439

pub_type

杂志文章

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