alpha 1-Adrenoceptors in the mammalian brain: similar pharmacology but different distribution in rodents and primates.
We have used membrane binding assays and in vitro autoradiographic techniques to study the characteristics and distribution of alpha 1-adrenoceptors in the brain of the rat, mouse, guinea pig, cat, pig, monkey and man. 125I-BE 2254 was used as ligand. The binding characteristics of alpha 1-adrenoceptors in the cortex of the rat and pig and the human cortex and hippocampus were fully comparable as shown by the binding profile of a series of alpha 1-adrenergic compounds. Differences were, however, seen in the densities of sites in human and rat hippocampus. Contrasting with the similarities seen in the pharmacological characteristics of alpha 1-adrenoceptors in the brain of several mammals, autoradiographic results showed dramatic differences in the regional distribution of brain alpha 1-adrenoceptors. While the thalamus and cortex were rich in alpha 1-sites in all the species investigated, differences in the nuclear and laminar distributions were seen between rodents and primates. One of the most important differences was the high density of alpha 1-adrenoceptors in the human and monkey hippocampus, mainly in the CA3, CA4 and dentate gyrus, while in all the other species investigated, the hippocampal formation was poor in these sites. These results suggest that, while alpha 1-adrenoceptors appear to be similar in their pharmacology, their distribution differs among these 6 mammals. Thus, different patterns of central activity can be expected from alpha 1-adrenergic drugs in the rodent and in the primate and man.
Palacios
J M
JM
Preclinical Research, Sandoz Ltd., Basle, Switzerland.
Hoyer
D
D
Cortés
R
R
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002415:Cats; D002540:Cerebral Cortex / Q000378:metabolism*; D006168:Guinea Pigs; D000882:Haplorhini; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D010627:Phenethylamines / Q000493:pharmacokinetics*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine; D044024:Tetralones
D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; C010652:BE 2254