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Effects of the somatostatin receptor subtype 4 selective agonist J‐2156 on sensory neuropeptide release and inflammatory reactions in rodents
Author(s) -
Helyes Z,
Pintér E,
Németh J,
Sándor K,
Elekes K,
Szabó Á,
Pozsgai G,
Keszthelyi D,
Kereskai L,
Engström M,
Wurster S,
Szolcsányi J
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706876
Subject(s) - somatostatin , substance p , neurogenic inflammation , calcitonin gene related peptide , neuropeptide , chemistry , medicine , evans blue , endocrinology , somatostatin receptor , agonist , myeloperoxidase , capsaicin , receptor , inflammation , pharmacology
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 sst 4 /sst 1 receptors. This study investigates the effects of a high affinity, sst 4 ‐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‐1 β with ELISA. Key results: J‐2156 (10–2000 nM) diminished electrically‐evoked neuropeptide release in a concentration‐dependent manner. EC 50 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 μg 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‐1β production in the lung, but not IL‐1β‐ or zymosan‐induced leukocyte accumulation in the skin were significantly diminished by J‐2156. Conclusions and implications: J‐2156 acting on sst 4 receptors inhibits neuropeptide release, vascular components of acute inflammatory processes, endotoxin‐induced granulocyte accumulation and IL‐1β 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. British Journal of Pharmacology (2006) 149 , 405–415. doi: 10.1038/sj.bjp.0706876