Beta-adrenoceptors in human brain labelled with [3H]dihydroalprenolol and [3H]CGP 12177.
beta-Adrenoceptor binding sites were characterised and quantitated in post-mortem human brain with [3H]dihydroalprenolol ([3H]DHA) and [3H]CGP 12177. In cerebral cortex, isoprenaline and propranolol displaced both radioligands with uniform affinity. Practolol and CGP 20712A (selective beta 1-adrenoceptor antagonists) displaced with high affinity from a greater proportion of sites than ICI 118,551 and IPS 339 (selective beta 2-adrenoceptor antagonists). In cerebellum, propranolol displaced both radioligands with uniform affinity. ICI 118,551 displaced with high affinity from a greater proportion of sites than CGP 20712A. The density of total beta-adrenoceptors (defined with isoprenaline) and of beta 1- and beta 2-adrenoceptors (defined with CGP 20712A and ICI 118,551 respectively) was studied by saturation binding of both radioligands in 13 brain areas. beta-Adrenoceptor density was higher in caudate, putamen and nucleus accumbens (100-120 fmol/mg protein) than cortex (50-70 fmol/mg protein) and densities were lowest in hypothalamus and cerebellum (27-38 fmol/mg protein). The proportion of beta 1-adrenoceptors (as a % of total beta-adrenoceptors) was high in caudate (80%), putamen (80%) and cortex (60-70%) and lower in hippocampus (40%) and cerebellum (30%). Both radioligands labelled a very similar number of beta-adrenoceptors in all brain regions studied.
De Paermentier
F
F
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, U.K.
Cheetham
S C
SC
Crompton
M R
MR
Horton
R W
RW
D000319:Adrenergic beta-Antagonists; D000526:Alprenolol / Q000031:analogs & derivatives*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D004082:Dihydroalprenolol; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D011217:Practolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D004082:Dihydroalprenolol; D000526:Alprenolol; D011433:Propranolol; C049763:CGP 20712A; D007545:Isoproterenol; C033394:CGP 12177; D011217:Practolol