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Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice

Department of Pharmacology and Pharmacotherapy, Institute of Pharmacognosy, Analgesic Research Laboratory of Gedon Richter Plc., University of Pécs, H-7624 Pécs, Hungary.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 08/2009; 106(31):13088-13093. DOI: 10.1073/pnas.0900681106

ABSTRACT We have shown that somatostatin released from activated capsaicin-sensitive nociceptive nerve endings during inflammatory
processes elicits systemic anti-inflammatory and analgesic effects. With the help of somatostatin receptor subtype 4 gene–deleted
mice (sst4−/−), we provide here several lines of evidence that this receptor has a protective role in a variety of inflammatory disease
models; several symptoms are more severe in the sst4 knockout animals than in their wild-type counterparts. Acute carrageenan-induced paw edema and mechanical hyperalgesia, inflammatory
pain in the early phase of adjuvant-evoked chronic arthritis, and oxazolone-induced delayed-type hypersensitivity reaction
in the skin are much greater in mice lacking the sst4 receptor. Airway inflammation and consequent bronchial hyperreactivity elicited by intranasal lipopolysaccharide administration
are also markedly enhanced in sst4 knockouts, including increased perivascular/peribronchial edema, neutrophil/macrophage infiltration, mucus-producing goblet
cell hyperplasia, myeloperoxidase activity, and IL-1β, TNF-α, and IFN-γ expression in the inflamed lung. It is concluded that
during these inflammatory conditions the released somatostatin has pronounced counterregulatory effects through sst4 receptor activation. Thus, this receptor is a promising novel target for developing anti-inflammatory, analgesic, and anti-asthmatic
drugs.

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