{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T04:32:15Z","timestamp":1761971535554,"version":"build-2065373602"},"reference-count":64,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T00:00:00Z","timestamp":1342656000000},"content-version":"vor","delay-in-days":6319,"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":[[1995,4]]},"abstract":"<jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Contraction of the rabbit isolated saphenous vein is mediated by a heterogeneous endothelin (ET) receptor population. This study has characterized these receptor subtypes by use of several pharmacologically distinct ET receptor agonists and antagonists.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ET\u20101, ET\u20103, sarafotoxin S6c (STXc) and [Ala<jats:sup>3,11<\/jats:sup>]ET\u2010l produced biphasic, concentration\u2010dependent contractions of the saphenous vein, responses which were best fitted by a two\u2010site model comprised of a high (pM) and a low (nM) affinity site. In contrast, IRL 1620 only recognized one of these sites. ET<jats:sub>(16\u201321)<\/jats:sub> was devoid of contractile activity. ET\u20101, ET\u20103 and STXc were equipotent at the high affinity site (pD<jats:sub>2<\/jats:sub>s of 12.0 \u00b1 0.2, 12.2 \u00b1 0.2 and 12.3 \u00b1 0.3) indicating that this site had the characteristics of an ET<jats:sub>B<\/jats:sub> receptor. In contrast, the low affinity site had the functional characteristics of an ET<jats:sub>C<\/jats:sub> receptor since the pD<jats:sub>2<\/jats:sub>s for ET\u20103 (10.2 \u00b10.3) and STXc (10.6 \u00b10.3) were significantly greater than that for ET\u20101 (9.1 \u00b10.1). These contractile responses were insensitive to BQ\u2010123, confirming that ET<jats:sub>A<\/jats:sub> receptors were not involved in mediating this effect.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>SB 209670 differentially antagonized the high affinity phases of the isopeptide concentration\u2010response curves in a fashion dependent on the competing agonist: relative to the K<jats:sub>B<\/jats:sub> obtained against STX<jats:sub>c<\/jats:sub> (0.15 nM). SB 209670 was 10 fold less potent when ET\u20101 was used as the competing agonist. This differential effect was not evident at the low affinity site (K<jats:sub>B<\/jats:sub> = 38 nM). SB 209670 produced parallel, concentration\u2010dependent rightward shifts in the concentration\u2010response curve to STXc Ro 47\u20130203 was approximately 1 to 2 orders of magnitude less potent than SB 209670 at inhibiting the high affinity component of the concentration\u2010response curve to STXc, whereas BQ\u2010788 and Ro 46\u20132005 were approximately 3 orders of magnitude less potent than SB 209670. In addition to RES\u2010701 and BQ\u2010123, the high affinity site was insensitive to PD 142893 suggesting that it may represent an ET<jats:sub>B2<\/jats:sub> receptor. Ro 47\u20130203 and SB 209670 were equipotent at inhibiting the low affinity component of the STX<jats:sub>c<\/jats:sub> concentration\u2010response curve. Although Ro 46\u20132005, BQ\u2010788, PD 142893 and RES\u2010701 produced significant antagonism at the low affinity site, they were at least ten fold less potent than SB 209670.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ET\u20101, ET\u20103 and STX<jats:sub>c<\/jats:sub> produced endothelium\u2010dependent vasorelaxation in the precontracted saphenous vein. Antagonist IC<jats:sub>50<\/jats:sub>s were approximated as being: SB 209670, 3 nM; BQ\u2010788 and RES 701, 300 nM; Ro 46\u20132005 and PD 142893, 3\u03bc<jats:sc>m<\/jats:sc> BQ\u2010123, \u2264 10\u03bc<jats:sc>m<\/jats:sc>, consistent with vasorelaxation being mediated by an ET<jats:sub>Bl<\/jats:sub> receptor.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In summary, three pharmacologically distinct ET receptor subtypes have been identified in the rabbit saphenous vein. Two contractile receptors are present on the vascular smooth muscle, a high affinity site with the characteristics of an ET<jats:sub>B2<\/jats:sub> receptor and a distinct lower affinity site with the characteristics of an ET<jats:sub>C<\/jats:sub> receptor. In addition, an ET<jats:sub>B1<\/jats:sub> receptor is present on the endothelium which mediates the vasodilator actions of this peptide family.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1111\/j.1476-5381.1995.tb14936.x","type":"journal-article","created":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T04:14:52Z","timestamp":1342757692000},"page":"1529-1540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Pharmacological evidence for the presence of three distinct functional endothelin receptor subtypes in the rabbit lateral saphenous vein"],"prefix":"10.1111","volume":"114","author":[{"given":"Stephen A.","family":"Douglas","sequence":"first","affiliation":[]},{"suffix":"Jr.","given":"George R.","family":"Beck","sequence":"additional","affiliation":[]},{"given":"John D.","family":"Elliott","sequence":"additional","affiliation":[]},{"given":"Eliot H.","family":"Ohlstein","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2012,7,19]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.4.500"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/348730a0"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1139\/y93-122"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)91010-K"},{"key":"e_1_2_1_6_1","first-page":"15P","article-title":"Heterogeneity of endothelin\/sarafotoxin receptors mediating contractions of the human isolated coronary artery","volume":"111","author":"BAX W.A.","year":"1994","journal-title":"Br. 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