{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:39:46Z","timestamp":1791171586541,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"31","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,8,4]]},"abstract":"<jats:p>\n                    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\u2013deleted mice (sst\n                    <jats:sub arrange=\"stagger\">4<\/jats:sub>\n                    <jats:sup arrange=\"stagger\">\u2212\/\u2212<\/jats:sup>\n                    ), 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 sst\n                    <jats:sub>4<\/jats:sub>\n                    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 sst\n                    <jats:sub>4<\/jats:sub>\n                    receptor. Airway inflammation and consequent bronchial hyperreactivity elicited by intranasal lipopolysaccharide administration are also markedly enhanced in sst\n                    <jats:sub>4<\/jats:sub>\n                    knockouts, including increased perivascular\/peribronchial edema, neutrophil\/macrophage infiltration, mucus-producing goblet cell hyperplasia, myeloperoxidase activity, and IL-1\u03b2, TNF-\u03b1, and IFN-\u03b3 expression in the inflamed lung. It is concluded that during these inflammatory conditions the released somatostatin has pronounced counterregulatory effects through sst\n                    <jats:sub>4<\/jats:sub>\n                    receptor activation. Thus, this receptor is a promising novel target for developing anti-inflammatory, analgesic, and anti-asthmatic drugs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0900681106","type":"journal-article","created":{"date-parts":[[2009,7,21]],"date-time":"2009-07-21T21:07:45Z","timestamp":1248210465000},"page":"13088-13093","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":92,"title":["Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice"],"prefix":"10.1073","volume":"106","author":[{"given":"Zsuzsanna","family":"Helyes","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Pint\u00e9r","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"S\u00e1ndor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriszti\u00e1n","family":"Elekes","sequence":"additional","affiliation":[{"name":"Institute of Pharmacognosy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1gnes","family":"B\u00e1nv\u00f6lgyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1niel","family":"Keszthelyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Sz\u0151ke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1niel M.","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Analgesic Research Laboratory of Gedon Richter Plc., and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"S\u00e1ndor","sequence":"additional","affiliation":[{"name":"Analgesic Research Laboratory of Gedon Richter Plc., and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Kereskai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Pozsgai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy P.","family":"Allen","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge CB22 3AT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piers C.","family":"Emson","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge CB22 3AT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienn","family":"Markovics","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Szolcs\u00e1nyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,8,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701685"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702144"},{"key":"e_1_3_3_3_2","first-page":"113","volume-title":"Hyperalgesia: Molecular Mechanisms and Clinical Implications","author":"Szolcs\u00e1nyi J","year":"2004","unstructured":"J Szolcs\u00e1nyi, E Pint\u00e9r, Z Helyes, Sensocrine function of capsaicin-sensitive nociceptors mediated by somatostatin regulates against inflammation and hyperalgesia. Hyperalgesia: Molecular Mechanisms and Clinical Implications, eds HO Handwerker, K Brune (IASP Press, Seattle), pp. 113\u2013128 (2004)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2006.04.010"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(76)90008-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)61790-2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051307"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20184"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00406.2006"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(95)02082-T"},{"key":"e_1_3_3_11_2","first-page":"161","article-title":"Somatostatin and somatostatin receptors in the immune system: A review","volume":"11","author":"ten Bokum AM","year":"2000","unstructured":"AM ten Bokum, LJ Hofland, PM van Hagen, Somatostatin and somatostatin receptors in the immune system: A review. Eur Cytokine Netw 11, 161\u2013176 (2000).","journal-title":"Eur Cytokine Netw"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(94)E0017-B"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1994.tb00972.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)88988-9"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704396"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-002-0563-9"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02629.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.24.5080"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706876"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.03.082"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.09.033"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2006.12.018"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.08.012"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(96)12766-X"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23168"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2454::AID-IMMU2454>3.0.CO;2-H"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(11)80303-7"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000097239"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-0115(92)90512-S"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.6.2955"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2004.10.013"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00918978"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350402"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(99)00083-2"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2007.08.018"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1610167"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.52.605"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(86)90574-6"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-21-09271.1999"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.25.4.4505"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0900681106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T17:02:38Z","timestamp":1653325358000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0900681106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,4]]},"references-count":40,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2009,8,4]]}},"alternative-id":["10.1073\/pnas.0900681106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0900681106","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,4]]},"assertion":[{"value":"2009-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-08-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}