{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T13:39:43Z","timestamp":1771853983333,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":150,"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":[[2008,9]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>The internal anal sphincter has been shown to contract in response to \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor stimulation and therefore \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor agonists may be useful in treating faecal incontinence. This study characterizes the \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor subtype responsible for mediating contraction of the internal anal sphincter of the pig.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>The potency of agonists and the affinities of several receptor subtype selective antagonists were determined on smooth muscle strips for the pig internal anal sphincter. Cumulative concentration\u2013response curves were performed using phenylephrine and noradrenaline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>The potency of the \u03b1<jats:sub>1A<\/jats:sub>\u2010adrenoceptor selective agonist A61603 (pEC<jats:sub>50<\/jats:sub>=7.79\u00b10.04) was 158\u2010fold greater than that for noradrenaline (pEC<jats:sub>50<\/jats:sub>=5.59\u00b10.02). Phenylephrine (pEC<jats:sub>50<\/jats:sub>=5.99\u00b10.05) was 2.5\u2010fold more potent than noradrenaline. The \u03b1<jats:sub>1D<\/jats:sub>\u2010adrenoceptor selective antagonist BMY7378 caused rightward shifts of the concentration\u2013response curves to phenylephrine and noradrenaline, yielding low affinity estimates of 6.59\u00b10.15 and 6.33\u00b10.13, respectively. Relatively high affinity estimates were obtained for the \u03b1<jats:sub>1A<\/jats:sub>\u2010adrenoceptor selective antagonists, RS100329 (9.01\u00b10.14 and 9.06\u00b10.22 with phenylephrine and noradrenaline, respectively) and 5\u2010methylurapidil (8.51\u00b10.10 and 8.31\u00b10.10, respectively). Prazosin antagonized responses of the sphincter to phenylephrine and noradrenaline, yielding mean affinity estimates of 8.58\u00b10.10 and 8.15\u00b10.08, respectively. The Schild slope for prazosin with phenylephrine was equal to unity (1.01\u00b10.24), however the Schild slope using noradrenaline was significantly less than unity (0.50\u00b10.11,<jats:italic>P<\/jats:italic>&lt;0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and implications:<\/jats:title><jats:p>The results suggest that contraction of circular smooth muscle from the pig internal anal sphincter is mediated via a population of adrenoceptors with the pharmacological characteristics of the \u03b1<jats:sub>1A\/L<\/jats:sub>\u2010adrenoceptor, most probably the \u03b1<jats:sub>1L<\/jats:sub>\u2010adrenoceptor form of this receptor.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2008)<jats:bold>155<\/jats:bold>, 110\u2013117; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.217\">10.1038\/bjp.2008.217<\/jats:ext-link>; published online 2 June 2008<\/jats:p><\/jats:sec>","DOI":"10.1038\/bjp.2008.217","type":"journal-article","created":{"date-parts":[[2008,6,2]],"date-time":"2008-06-02T10:15:03Z","timestamp":1212401703000},"page":"110-117","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Characterization of the \u03b1<sub>1<\/sub>\u2010adrenoceptor subtype mediating contractions of the pig internal anal sphincter"],"prefix":"10.1111","volume":"155","author":[{"given":"K A","family":"Mills","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Hausman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Chess\u2010Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01299816"},{"issue":"2","key":"e_1_2_7_3_1","first-page":"S1","article-title":"Guide to receptors and channels (GRAC), 3rd edn","volume":"153","author":"Alexander SPH","year":"2008","journal-title":"Br J Pharmacol"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2004.07.011"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-3150.2004.00475.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00755-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb16356.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2168.1999.01021.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02236550"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2168.2000.01306.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.48.3.356"},{"key":"e_1_2_7_13_1","first-page":"209","article-title":"RS 17053 (N\u2010[2\u2010(2\u2010cyclopropylmethoxyphenoxy)ethyl]\u20105\u2010chloro\u2010\u03b1,\u03b1\u2010dimethyl\u20101H\u2010indole\u20103\u2010ethanamine hydrochloride, a selective \u03b11A\u2010adrenoceptor antagonist, displays low affinity for functional \u03b11\u2010adrenoceptors in human prostate: implications for adrenoceptor classification","volume":"49","author":"Ford AP","year":"1996","journal-title":"Mol Pharmacol"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701207"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)00751-R"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb12005.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.5694\/j.1326-5377.2002.tb04283.x","article-title":"Prevalence of faecal incontinence and associated risk factors. 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