{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T16:46:19Z","timestamp":1768927579327,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,3,25]],"date-time":"2009-03-25T00:00:00Z","timestamp":1237939200000},"content-version":"vor","delay-in-days":5046,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology &amp; Toxicology"],"published-print":{"date-parts":[[1995,6]]},"abstract":"<jats:p><jats:bold>Abstract:<\/jats:bold>Simultaneous computer modelling of control and guanfacine\u2010masked [<jats:sup>3<\/jats:sup>H]\u2010MK 912 saturation curves as well as guanfacine competition curves revealed that both \u03b1<jats:sub>2A<\/jats:sub>\u2010 and \u03b1<jats:sub>2C<\/jats:sub>\u2010adrenoceptor subtypes were present in the guinea pig cerebral cortex. The K<jats:sub>d<\/jats:sub>value of [<jats:sub>3<\/jats:sub>H]\u2010MK 912 determined for the \u03b1<jats:sub>2A<\/jats:sub>\u2010subtype was 403 pM and for the \u03b1<jats:sub>2C<\/jats:sub>\u2010subtype 79.8 pM; the receptor sites showing capacities 172 and 19.5 fmol\/mg protein, respectively. The K<jats:sub>ds<\/jats:sub>of guanfacine were 20 and 880 nM for the \u03b1<jats:sub>2A<\/jats:sub>\u2010 and \u03b1<jats:sub>2C<\/jats:sub>\u2010adrenoceptor, respectively. In the guinea pig kidney [<jats:sub>3<\/jats:sub>H]\u2010MK 912 bound to a single saturable site with K<jats:sub>d<\/jats:sub>8.34 nM and capacity 285 fmol\/mg protein, the site showing pharmacological properties like an \u03b1<jats:sub>2B<\/jats:sub>\u2010adrenoceptor. Binding constants of 22 compounds for the three guinea pig \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor subtypes were determined by computer modelling competition curves using for the cerebral cortex a \u201c3\u2010curve assay\u201d, for the kidney an \u201c1\u2010curve assay\u201d, and using [<jats:sup>3<\/jats:sup>H]\u2010MK 912 as labelled ligand. Of the tested drugs guanfacine and BRL 44408 were found to be clearly \u03b1<jats:sub>2A<\/jats:sub>\u2010selective. Spiroxatrine, yohimbine, rauwolscine and WB 4101, as well as [<jats:sub>3<\/jats:sub>H]\u2010MK 912 itself, were found to be \u03b1<jats:sub>2C<\/jats:sub>\u2010selective. The most selective compounds for \u03b1<jats:sub>2B<\/jats:sub>\u2010adrenoceptors, when compared to \u03b1<jats:sub>2A<\/jats:sub>\u2010adrenoceptors, were ARC 239 and prazosin. In the guinea pig kidney [<jats:sub>3<\/jats:sub>H]\u2010p\u2010aminoclonidine bound to \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors as well as to non\u2010adrenergic imidazoline sites. The \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors could be completely blocked using 10 \u03bcM (\u2010)\u2010adrenaline without the non\u2010adrenergic sites being affected. During these conditions the analysis of combined saturation and competition studies using labelled and unlabeled p\u2010aminoclonidine with computer modelling revealed that the ligand labelled two different sites with K<jats:sub>ds<\/jats:sub>of 310 and 47,000 nM, respectively. Competition curves of 16 compounds for the non\u2010adrenergic [<jats:sub>3<\/jats:sub>H]\u2010p\u2010aminoclonidine sites were shallow and resolved into two\u2010site fits. For the high affinity [<jats:sub>3<\/jats:sub>H]\u2010p\u2010aminoclonidine site the highest affinities were shown by 1\u2010medetomidine, UK\u201014,304, guanabenz and detomidine; the K<jats:sub>ds<\/jats:sub>of these drugs ranging 26\u201372 nM. All drugs tested showed low but varying affinities for the low affinity [<jats:sub>3<\/jats:sub>H]\u2010p\u2010aminoclonidine site. These data indicated that the [<jats:sup>3<\/jats:sup>H]\u2010p\u2010aminoclonidine binding sites of the guinea pig kidney are grossly different from the [<jats:sub>3<\/jats:sub>H]\u2010idazoxan binding I<jats:sub>2<\/jats:sub>\u2010receptors previously demonstrated also to be present in the guinea pig kidney.<\/jats:p>","DOI":"10.1111\/j.1600-0773.1995.tb00161.x","type":"journal-article","created":{"date-parts":[[2009,3,25]],"date-time":"2009-03-25T18:57:59Z","timestamp":1238007479000},"page":"353-364","source":"Crossref","is-referenced-by-count":51,"title":["Comparison of the Binding Activities of Some Drugs on \u03b1<sub>2A<\/sub>, \u03b1<sub>2B<\/sub>and \u03b1<sub>2C<\/sub>\u2010Adrenoceptors and Non\u2010Adrenergic Imidazoline Sites in the Guinea Pig"],"prefix":"10.1111","volume":"76","author":[{"given":"Staffan","family":"Uhl\u00e9n","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruta","family":"Muceniece","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ninfa","family":"Rangel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar","family":"Tiger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarl E. 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