title: Alpha 1-adrenoceptors: the ability of various agonists and antagonists to discriminate between two distinct [3H]prazosin binding sites.
abstract: Recently, it has been demonstrated that two distinct alpha 1-adrenoceptor binding sites showing high and low affinity for WB-4101 (2-(2,6-dimethoxyphenoxy)ethyl-aminomethyl-1,4-benzodioxane) and 5-methyl-urapidil can be distinguished. In the present study we examined the ability of several agonists and antagonists to discriminate between these alpha 1-adrenoceptor binding sites. [3H]Prazosin binding to membranes of rat liver, heart, cerebral cortex and hippocampus was inhibited monophasically by butanserine, I-BE 2254 (2-(3-(4-hydroxy-3-iodophenyl)ethylaminomethyl)tetralone-hydrochloride), prazosin, rauwolscine and verapamil. In contrast, competition curves of adrenaline, oxymetazoline, amidephrine and YM-12617 (5-[2-[[2-(o-ethoxy-phenoxy)ethyl]-amino]propyl]-2- methoxybenzenesulfonamide HCl) were best described by a model of two binding sites. Chloroethylclonidine (CEC), a compound shown to irreversibly eliminate binding sites with low affinity for WB-4101, increased the proportion of high affinity binding sites for oxymetazoline and amidephrine, whereas the binding data for prazosin and adrenaline remained unchanged. These results indicate that amidephrine, oxymetazoline and YM-12617, but not the other drugs tested discriminate between different alpha 1-adrenoceptor recognition sites labelled by [3H]prazosin.
authors.affiliation: Institut für Pharmakologie, Universitätsklinikum Essen, FRG.
authors.forename: G
authors.initials: G
authors.lastname: Hanft
authors.forename: G
authors.initials: G
authors.lastname: Gross
authors.forename: J J
authors.initials: JJ
authors.lastname: Beckeringh
authors.forename: C
authors.initials: C
authors.lastname: Korstanje
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects*; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D011224:Prazosin