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This study investigates the effects of a high affinity, sst<jats:sub>4<\/jats:sub>\u2010selective, synthetic agonist, J\u20102156, on sensory neuropeptide release <jats:italic>in vitro<\/jats:italic> and inflammatory processes <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Electrically\u2010induced SP, CGRP and somatostatin release from isolated rat tracheae was measured with radioimmunoassay. Mustard oil\u2010induced neurogenic inflammation in rat hindpaw skin was determined by Evans blue leakage and in the mouse ear with micrometry. Dextran\u2010, carrageenan\u2010 or bradykinin\u2010induced non\u2010neurogenic inflammation was examined with plethysmometry or Evans blue, respectively. Adjuvant\u2010induced chronic arthritis was assessed by plethysmometry and histological scoring. Granulocyte accumulation was determined with myeloperoxidase assay and IL\u20101<jats:italic>\u03b2<\/jats:italic> with ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>J\u20102156 (10\u20132000\u2003nM) diminished electrically\u2010evoked neuropeptide release in a concentration\u2010dependent manner. EC<jats:sub>50<\/jats:sub> for the inhibition of substance P, CGRP and somatostatin release were 11.6\u2003nM, 14.3\u2003nM and 110.7\u2003nM, respectively. J\u20102156 (1\u2013100\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup> i.p.) significantly, but not dose\u2010dependently, inhibited neurogenic and non\u2010neurogenic acute inflammatory processes and adjuvant\u2010induced chronic oedema and arthritic changes. Endotoxin\u2010evoked myeloperoxidase activity and IL\u20101\u03b2 production in the lung, but not IL\u20101\u03b2\u2010 or zymosan\u2010induced leukocyte accumulation in the skin were significantly diminished by J\u20102156.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>J\u20102156 acting on sst<jats:sub>4<\/jats:sub> receptors inhibits neuropeptide release, vascular components of acute inflammatory processes, endotoxin\u2010induced granulocyte accumulation and IL\u20101\u03b2 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\u2010inflammatory drugs.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2006) <jats:bold>149<\/jats:bold>, 405\u2013415. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706876\">10.1038\/sj.bjp.0706876<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0706876","type":"journal-article","created":{"date-parts":[[2006,9,4]],"date-time":"2006-09-04T14:08:25Z","timestamp":1157378905000},"page":"405-415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Effects of the somatostatin receptor subtype 4 selective agonist J\u20102156 on sensory neuropeptide release and inflammatory reactions in 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