{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T01:55:06Z","timestamp":1700618106099},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":486,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Acute intraperitoneal (i.p.) administration of cholecystokinin (CCK) is known to induce a significant, but short\u2010lasting, reduction in food intake, followed by recovery within hours. Therefore, we had covalently coupled CCK to a 10\u2003kDa polyethylene glycol and showed that this conjugate, PEG\u2010CCK<jats:sub>9<\/jats:sub>, produced a significantly longer anorectic effect than unmodified CCK<jats:sub>9<\/jats:sub>. The present study assessed the dose\u2013dependency of this response and the effect of two selective CCK<jats:sub>1<\/jats:sub> receptor antagonists, with different abilities to cross the blood\u2010brain barrier (BBB), on PEG\u2010CCK<jats:sub>9<\/jats:sub>\u2010induced anorexia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Food intake was measured, for up to 23 h, after i.p. administration of different doses (2, 4, 8, 16 and 32 <jats:italic>\u03bc<\/jats:italic>g kg<jats:sup>\u22121<\/jats:sup>) of CCK<jats:sub>9<\/jats:sub> or PEG\u2010CCK<jats:sub>9<\/jats:sub> in male Wistar rats. Devazepide (100 <jats:italic>\u03bc<\/jats:italic>g kg<jats:sup>\u22121<\/jats:sup>), which penetrates the BBB or 2\u2010NAP (3 mg kg<jats:sup>\u22121<\/jats:sup>), which does not cross the BBB, were coadministered i.p. with PEG\u2010CCK<jats:sub>9<\/jats:sub> (6 <jats:italic>\u03bc<\/jats:italic>g kg<jats:sup>\u22121<\/jats:sup>) and food intake was monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>In PEG\u2010CCK<jats:sub>9<\/jats:sub>\u2010treated rats, a clear dose\u2010dependency was seen for both the duration and initial intensity of the anorexia whereas, for CCK<jats:sub>9<\/jats:sub>, only the initial intensity was dose\u2010dependent. Intraperitoneal administration of devazepide or 2\u2010NAP, injected immediately prior to PEG\u2010CCK<jats:sub>9<\/jats:sub>, completely abolished the anorectic effect of PEG\u2010CCK<jats:sub>9<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>The duration of the anorexia for PEG\u2010CCK<jats:sub>9<\/jats:sub> was dose\u2010dependent, suggesting that PEGylation of CCK<jats:sub>9<\/jats:sub> increases its circulation time. Both devazepide and 2\u2010NAP completely abolished the anorectic effect of i.p. PEG\u2010CCK<jats:sub>9<\/jats:sub> indicating that its anorectic effect was solely due to stimulation of peripheral CCK<jats:sub>1<\/jats:sub> receptors.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2007) <jats:bold>152<\/jats:bold>, 396\u2013403; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707390\">10.1038\/sj.bjp.0707390<\/jats:ext-link>; published online 9 July 2007<\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707390","type":"journal-article","created":{"date-parts":[[2007,7,9]],"date-time":"2007-07-09T08:46:18Z","timestamp":1183970778000},"page":"396-403","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["PEGylated cholecystokinin prolongs satiation in rats: dose dependency and receptor 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