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Vasculoprotective effects of somatostatin receptor subtypes.

Abstract：

:We have shown that somatostatin agonist peptide CH275, selective to somatostatin receptor (sst) subtypes 1,4, was more effective in preventing intimal hyperplasia than the sst2,3,5-selective octreotide, raising the question what are the separate roles of the sst1- and 4-subtypes. Here, we dissect this observation further with highly subtype-selective peptidomimetics and demonstrate that, after rat carotid denudation, both the sst1- and 4-selective analogs (300 microg/kg/day, s.c.) increased lumen size, while only the sst4-selective analog significantly reduced intimal nuclei number, intimal area, and intima/media ratio. The 2,3,5-selective compounds had no effect on these parameters. The observed in vivo effects were further investigated ex vivo with explant outgrowth from pieces of vascular wall. The sst4-selective analog was more effective than the sst1-selective one in inhibiting the percent of outgrowth and the migration of cells from the explants while neither compound affected proliferation. Thus, selective targeting to sst4 should be considered when developing orally active vasculoprotective therapies.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Tigerstedt NM,Aavik E,Aavik S,Savolainen-Peltonen H,Hayry P

doi

10.1016/j.mce.2007.08.018

subject

Has Abstract

pub_date

2007-12-15 00:00:00

pages

34-8

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(07)00339-5

journal_volume

279

pub_type

杂志文章

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