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Effects of the somatostatin receptor subtype 4 selective agonist J-2156 on sensory neuropeptide release and inflammatory reactions in rodents.

Abstract：

BACKGROUND AND PURPOSE:Substance P (SP) and calcitonin gene-related peptide (CGRP) released from capsaicin-sensitive sensory nerves induce local neurogenic inflammation; somatostatin exerts systemic anti-inflammatory actions presumably via sst4/sst1 receptors. This study investigates the effects of a high affinity, sst4-selective, synthetic agonist, J-2156, on sensory neuropeptide release in vitro and inflammatory processes in vivo. EXPERIMENTAL APPROACH:Electrically-induced SP, CGRP and somatostatin release from isolated rat tracheae was measured with radioimmunoassay. Mustard oil-induced neurogenic inflammation in rat hindpaw skin was determined by Evans blue leakage and in the mouse ear with micrometry. Dextran-, carrageenan- or bradykinin-induced non-neurogenic inflammation was examined with plethysmometry or Evans blue, respectively. Adjuvant-induced chronic arthritis was assessed by plethysmometry and histological scoring. Granulocyte accumulation was determined with myeloperoxidase assay and IL-1beta with ELISA. KEY RESULTS:J-2156 (10-2000 nM) diminished electrically-evoked neuropeptide release in a concentration-dependent manner. EC50 for the inhibition of substance P, CGRP and somatostatin release were 11.6 nM, 14.3 nM and 110.7 nM, respectively. J-2156 (1-100 microg kg(-1) i.p.) significantly, but not dose-dependently, inhibited neurogenic and non-neurogenic acute inflammatory processes and adjuvant-induced chronic oedema and arthritic changes. Endotoxin-evoked myeloperoxidase activity and IL-1beta production in the lung, but not IL-1beta- or zymosan-induced leukocyte accumulation in the skin were significantly diminished by J-2156. CONCLUSIONS AND IMPLICATIONS:J-2156 acting on sst4 receptors inhibits neuropeptide release, vascular components of acute inflammatory processes, endotoxin-induced granulocyte accumulation and IL-1beta synthesis in the lung and synovial and inflammatory cells in chronic arthritis. Therefore it might be a promising lead for the development of novel anti-inflammatory drugs.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Helyes Z,Pintér E,Németh J,Sándor K,Elekes K,Szabó A,Pozsgai G,Keszthelyi D,Kereskai L,Engström M,Wurster S,Szolcsányi J

doi

10.1038/sj.bjp.0706876

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

405-15

issue

eissn

0007-1188

issn

1476-5381

pii

0706876

journal_volume

149

pub_type

杂志文章

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Effects of the somatostatin receptor subtype 4 selective agonist J-2156 on sensory neuropeptide release and inflammatory reactions in rodents.