{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:53:07Z","timestamp":1764996787276},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":4392,"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":[[1997,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Although conscious dogs have often been used for colonic motility studies with 5\u2010hydroxytryptamine (5\u2010HT), the effects of 5\u2010HT on the isolated colon have not been thoroughly characterized yet. The current study was undertaken to characterize the response to 5\u2010HT of the canine isolated colon longitudinal muscle.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Longitudinal strips of canine midcolon deprived of (sub)mucosa were prepared for isotonic measurement. 5\u2010HT induced contractions from 3 nM onwards, which were not affected by selective inhibition of 5\u2010HT re\u2010uptake, monoamine oxidase or blockade of \u03b1\u2010adrenoceptors. Tetrodotoxin (0.3 \u03bcm) did not affect the responses to 5\u2010HT, suggesting that smooth muscle 5\u2010HT receptors are involved. The selective 5\u2010HT<jats:sub>4<\/jats:sub> receptor antagonist SB 204070 (10 nM) slightly enhanced contractions to 5\u2010HT and therefore it was included in the organ bath solution in all further experiments. The 5\u2010HT<jats:sub>1<\/jats:sub> and 5\u2010HT<jats:sub>2<\/jats:sub> receptor antagonist methysergide (0.1 \u03bcm) depressed the curve to 5\u2010HT, but the selective 5\u2010HT<jats:sub>3<\/jats:sub> receptor antagonist granisetron (0.3 \u03bcm) had no effect.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Besides 5\u2010HT, \u03b1\u2010methyl\u20105\u2010HT (\u03b1\u2010Me\u20105\u2010HT), 5\u2010methoxytryptamine (5\u2010MeOT), 2\u2010methyl\u20105\u2010HT (2\u2010Me\u20105\u2010HT) and 5\u2010carboxamidotryptamine (5\u2010CT) also induced contractions, with the following rank order of potency (pEC<jats:sub>50<\/jats:sub> values in parentheses): 5\u2010HT (6.9) = \u03b1\u2010methyl\u20105\u2010HT (6.9) &gt;2\u2010Me\u20105\u2010HT (5.8) = 5\u2010MeOT (5.7) = 5\u2010CT (5.6), indicative of 5\u2010HT<jats:sub>2<\/jats:sub> receptor involvement. \u03b1\u2010Me\u20105\u2010HT produced a bell\u2010shaped curve, which was not affected by \u03b1\u2010adrenoceptor blockade. 5\u2010HT, 5\u2010MeOT, 2\u2010Me\u20105\u2010HT and 5\u2010CT produced a monophasic concentration\u2010response curve, consistent with an interaction with a single receptor site. 8\u2010Hydroxy\u20102\u2010(di\u2010n\u2010propylamino) tetralin (8\u2010OH\u2010DPAT) and tryptamine only induced contractions at a concentration exceeding 1 \u03bcM.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The selective 5\u2010HT<jats:sub>2B<\/jats:sub> receptor antagonist SB 204741 (0.3 \u03bcM) did not affect the curve to 5\u2010HT. Ketanserin, cisapride and spiroxatrine behaved as competitive antagonists with p <jats:italic>K<\/jats:italic><jats:sub>b<\/jats:sub> values of, respectively, 8.4, 8.1 and 6.7. Spiroxatrine (1 \u03bcm) shifted the curve to 5\u2010MeOT rightward yielding an apparent pA<jats:sub>2<\/jats:sub> of 7.1. Other antagonists at 5\u2010HT<jats:sub>2A<\/jats:sub> receptors also surmountably inhibited the contractions to 5\u2010HT (apparent pA<jats:sub>2<\/jats:sub> value in parentheses): mesulergine (8.2), cinanserin (8.2), yohimbine (6.2) and mianserin (8.6). However, as well as a rightward shift, methiothepin (8.3), pizotifen (8.6) and spiperone (8.8) also caused a depression of the curve, indicative of \u2018pseudo\u2010irreversible\u2019 antagonism. Taken together, the above mentioned affinity estimates most closely corresponded to literature affinity values for 5\u2010HT<jats:sub>2A<\/jats:sub> receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It was concluded that 5\u2010HT induces contractions of the canine midcolon longitudinal muscle primarily by stimulation of smooth muscle 5\u2010HT<jats:sub>2A<\/jats:sub> receptors. The presence of inhibitory 5\u2010HT<jats:sub>4<\/jats:sub> receptors cannot be ruled out.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0700954","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T16:10:13Z","timestamp":1156522213000},"page":"714-720","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Characterization of the contraction to 5\u2010HT in the canine colon longitudinal muscle"],"prefix":"10.1111","volume":"120","author":[{"given":"Nicolaas H.","family":"Prins","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel R.","family":"Briejer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan A.J.","family":"Schuurkes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_5_3_1","first-page":"652","article-title":"Pharmacological characterization of 5\u2010hydroxytrypta\u2010mine receptors in the canine terminal ileum and ileocolonic junction","volume":"254","author":"Boeckxstaens G.E.","year":"1990","journal-title":"J. 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