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001-es BibID:	BIBFORM040213
Első szerző:	Helyes Zsuzsanna
Cím:	Effects of the somatostatin receptor subtype 4 selective agonist J-2156 on sensory neuropeptide release and inflammatory reactions in rodents / Z. Helyes, E. Pintér, J. Németh, K. Sándor, K. Elekes, A. Szabó, G. Pozsgai, D. Keszthelyi, L. Kereskai, M. Engström, S. Wurster, J. Szolcsányi
Dátum:	2006
ISSN:	0007-1188
Megjegyzések:	Substance P (SP) and calcitonin gene-related peptide (CGRP) released from capsaicin-sensitivesensory nerves induce local neurogenic inflammation; somatostatin exerts systemic anti-inflammatory actions presumably viasst4/sst1 receptors. This study investigates the effects of a high affinity, sst4-selective, synthetic agonist, J-2156, on sensoryneuropeptide release in vitro and inflammatory processes in vivo.Experimental approach: Electrically-induced SP, CGRP and somatostatin release from isolated rat tracheae was measuredwith radioimmunoassay. Mustard oil-induced neurogenic inflammation in rat hindpaw skin was determined by Evans blueleakage and in the mouse ear with micrometry. Dextran-, carrageenan- or bradykinin-induced non-neurogenic inflammationwas examined with plethysmometry or Evans blue, respectively. Adjuvant-induced chronic arthritis was assessed byplethysmometry and histological scoring. Granulocyte accumulation was determined with myeloperoxidase assay and IL-1bwith ELISA.Key results: J-2156 (10-2000 nM) diminished electrically-evoked neuropeptide release in a concentration-dependentmanner. EC50 for the inhibition of substance P, CGRP and somatostatin release were 11.6 nM, 14.3nM and 110.7 nM,respectively. J-2156 (1-100 mgkg-1 i.p.) significantly, but not dose-dependently, inhibited neurogenic and non-neurogenicacute inflammatory processes and adjuvant-induced chronic oedema and arthritic changes. Endotoxin-evoked myeloperoxidaseactivity and IL-1b production in the lung, but not IL-1b- or zymosan-induced leukocyte accumulation in the skin weresignificantly diminished by J-2156.Conclusions and implications: J-2156 acting on sst4 receptors inhibits neuropeptide release, vascular components of acuteinflammatory processes, endotoxin-induced granulocyte accumulation and IL-1b synthesis in the lung and synovial andinflammatory cells in chronic arthritis. Therefore it might be a promising lead for the development of novel anti-inflammatorydrugs.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	British Journal Of Pharmacology. - 149 : 4 (2006), p. 405-415. -
További szerzők:	Pintér E. Németh József (1954-) (vegyész, analitikus) Sándor K. Elekes K. Pozsgai Gábor Keszthelyi Dániel Kereskai László Engström, M. Wurster, S. Szolcsányi János (Pécs)
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