{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:34:52Z","timestamp":1780400092062,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":4303,"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":[[1997,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>We set out to ascertain the role of tachykinins, neurokinin A and substance P, in castor oil\u2010induced diarrhoea in rats as disclosed by the inhibitory effect of the non\u2010peptide NK<jats:sub>1<\/jats:sub>\u2010 and NK<jats:sub>2<\/jats:sub>\u2010receptor antagonists, SR 140333 and SR 48968, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>SR 48968 (0.02 to 20\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>, s.c. or p.o.), and the opioid receptor agonist loperamide (1\u201310\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, p.o.), dose\u2010dependently prevented castor oil effects: % inhibition vs castor oil, diarrhoea 0 to 100, increase in faecal mass 7 to 90 and water content 16 to 90. SR 140333 (0.02 to 20\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>, s.c.) and the platelet activating factor antagonist SR 27417 (5 to 500\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>, p.o.) did not prevent the increase in faecal water content, but reduced faecal mass (35 to 66%) and diarrhoea (0 to 57%).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The <jats:bold>R<\/jats:bold>\u2010enantiomers of tachykinin NK<jats:sub>1<\/jats:sub> and NK<jats:sub>2<\/jats:sub> receptor antagonists, SR 140603 and SR 48605 (both at 2 or 20\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>, s.c.) had no effect other than reducing faecal mass at the highest dose tested.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>SR 48968 (20\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>, p.o.) but not loperamide (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, p.o.) given 24\u2003h before castor oil, still slightly but significantly reduced by 30% the increase of faecal mass output; both treatments significantly reduced (30 to 70%) the effect of castor oil on faecal water content, although the incidence of diarrhoea was only slightly less than in controls.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In castor oil\u2010treated rats, naloxone (2\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, s.c.) completely blocked the antidiarrhoeal action of loperamide (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, p.o.) but not of SR 48968 (20\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>, p.o.); a similar result was obtained on faecal mass and water content.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Castor oil strongly increased the occurrence of manometrically recorded propulsive giant contractions (500 to 1000% over control values) of transverse and distal colon, this effect being significantly prevented (80 to 100%) by SR 48968 and loperamide and partially by SR 140333 (35% distal colon, 70% transverse colon).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In castor oil free rats, loperamide but not SR 48968 or SR 140333 significantly reduced by 50% the gastrointestinal transit of a charcoal test meal, as well as 24\u2003h faecal mass output. Consistently, loperamide, unlike the tachykinin receptor antagonists, had a dramatic effect on manometric recordings of intestinal motility, reducing all kinds of colonic contractions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our findings suggest that castor oil diarrhoea in rats entails activation of NK<jats:sub>1<\/jats:sub> and NK<jats:sub>2<\/jats:sub> receptors by endogenous tachykinins, whose antagonists may have a potential as antidiarrhoeal agents free from the constipating action of opioids.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701130","type":"journal-article","created":{"date-parts":[[2006,7,21]],"date-time":"2006-07-21T14:37:20Z","timestamp":1153492640000},"page":"375-380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Role of tachykinins in castor oil diarrhoea in rats"],"prefix":"10.1111","volume":"121","author":[{"given":"Tiziano","family":"Croci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Landi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Emonds\u2010Alt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Le Fur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pierre","family":"Maffrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Manara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80041-5"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000171327"},{"key":"e_1_2_5_4_1","first-page":"G329","article-title":"Cold\u2010restraint stress increases rat fecal pellet output and colonic transit","volume":"258","author":"Barone F.C.","year":"1990","journal-title":"Am. 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