title: Subtypes of alpha 1-adrenoceptors in hippocampus of pigs, guinea-pigs, calves and humans: regional differences.
abstract: Radioligand binding studies were performed with membranes of guinea-pig, pig, calf and human hippocampus using [125I]BE 2254 (also known as [125I]HEAT) as the radioligand. [125I]BE 2254 bound with similar high affinity to saturable populations of recognition sites in all four membrane preparations. Competition curves obtained with a variety of ligands (e.g., WB 4101, benoxathian, 5-methyl-urapidil) were biphasic and the profiles of the high- and low-affinity components of [125I]BE 2254 binding were similar in all four membrane preparations. The data suggest that [125I]BE 2254 labels two subtypes of alpha 1-adrenoceptors in the hippocampus of these species. [3H]WB 4101 was used to label alpha 1A recognition sites in pig hippocampus membranes. [3H]WB 4101 recognized with high affinity an apparently homogeneous class of sites, as suggested by monophasic saturation and competition experiments. The rank order of affinity of the compounds for the high-affinity component of [125I]BE 2254 binding was similar to the rank order of affinity of these drugs for [3H]WB 4101 sites. The pharmacological profile of the low-affinity component of [125I]BE 2254 binding was similar to that described recently for the alpha 1B-adrenoceptor cloned from DDT1 cells. In autoradiographic studies with human hippocampal slices, CEC (chloroethylclonidine), an alkylating agent described to show selectivity for alpha 1B-adrenoceptors, displaced preferentially [125I]BE 2254 binding from the molecular layer of the dentate gyrus. In contrast, WB 4101 an alpha 1A-adrenoceptor-selective ligand, displaced preferentially [125I]BE 2254 binding in the hilus and the CA3 region. The data show that 2 subtypes of alpha 1-adrenergic recognition sites can be identified in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Preclinical Research, Sandoz Ltd., Basel, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Hoyer
authors.forename: C R
authors.initials: CR
authors.lastname: Jones
authors.forename: W
authors.initials: W
authors.lastname: Ford
authors.forename: J M
authors.initials: JM
authors.lastname: Palacios
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D002417:Cattle; D004146:Dioxanes / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D010627:Phenethylamines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine; D044024:Tetralones
chemical_list: D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007457:Iodine Radioisotopes; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; C010652:BE 2254; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane