title: Pharmacological characterization and autoradiographic distribution of alpha2-adrenoceptor antagonist [3H]RX 821002 binding sites in the chicken brain.
abstract: Knowledge about the noradrenergic system in birds is very scarce even though their biological diversity and complex social behavior make them an excellent model for studying neuronal functions and developmental biology. While the role of norepinephrine has been described in depth in a large number of central and peripheral functions in mammals, reports for avian species are limited. The radioligand [(3)H]RX 821002 ([(3)H]1,4-[6,7(n)3H]-benzodioxan-2-methoxy-2-yl)-2-imidazol) has been used to map and characterize alpha(2)-adrenoceptors through the chicken brain using in vitro autoradiography and membrane homogenates binding assays. [(3)H]RX 821002 showed a saturable and high affinity binding to a site compatible with alpha(2)-adrenoceptor, and to a serotonergic component. The autoradiographic assays displayed a similar alpha(2)-adrenoceptor distribution than those previously reported in birds using other radioligands such as [(3)H]UK 14304 ([(3)H]5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine) or [(3)H]clonidine. [(3)H]RX 821002 binding pharmacological characterization was carried out in different chicken brain regions using membrane homogenates for competition assays with different alpha(2)-adrenoceptor agonists and antagonists drugs (oxymetazoline, BRL 44408 [2-(2H-(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidazole] ARC 239 [2-(2-4-(O-methoxyphenyl)-piperazin-1-yl)-ethyl-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione], prazosin, UK 14304 and RX 821002). The results showed alpha(2A) as the predominant alpha(2)-adrenoceptor subtype in the chicken brain while alpha(2B)- and/or alpha(2C)-adrenoceptor subtypes were detected only in the telencephalon. RX 821002, serotonin (5-HT) and 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] competition assays, and competition binding assays performed in the presence of serotonin demonstrated that [(3)H]RX 821002 binds with higher affinity to a serotonergic component, probably 5-HT(1A) receptors, than to the alpha(2)-adrenoceptors. Similar pharmacological properties for the alpha(2)-adrenoceptor component were observed both in rat and chicken brain. The results demonstrate that the different alpha(2)-adrenoceptor subtypes are present in chicken brain and suggest that these receptors are highly conserved through evolution.
authors.affiliation: Department of Cell Biology and Anatomy, Faculty of Biological and Environmental Sciences, University of Leon, Leon 24071, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Díez-Alarcia
authors.forename: F
authors.initials: F
authors.lastname: Pilar-Cuéllar
authors.forename: M A
authors.initials: MA
authors.lastname: Paniagua
authors.forename: J J
authors.initials: JJ
authors.lastname: Meana
authors.forename: A
authors.initials: A
authors.lastname: Fernández-López
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects*; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019329:Idazoxan / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010109:Oxymetazoline / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D014316:Tritium; D012701:Serotonin; D010109:Oxymetazoline; C058525:2-methoxyidazoxan; D019329:Idazoxan