Labelling of rat brain beta-adrenoceptors: (3H)CGP-12177 or (125I)iodocyanopindolol?
Binding of (125I)iodocyanopindolol (ICYP) and (3H)CGP-12177 to rat brain homogenates was characterized and compared. ICYP was shown to bind to both beta-adrenergic and serotonin1B (5HT1B) receptors whereas (3H)CGP-12177 only labelled the first ones. The addition of 10 microM serotonin (5HT) prevented ICYP binding to 5HT receptors and under these experimental conditions both ligands labelled a similar total number of beta-adrenoceptors in the different rat brain regions. ICYP displayed a higher affinity for cerebellar (mainly beta 2-subtype) than for cerebral cortex beta-adrenoceptors (mainly beta 1-subtype) suggesting a subtype selectivity. A multiple displacement binding approach using CGP-20712A, a beta 1-subtype ligand, as competitor revealed a 2.6 fold selectivity of ICYP for the beta 2-adrenoceptor subtype. On the other hand, (3H)CGP-12177 binds only to beta-adrenoceptors and is not subtype selective in the rat brain homogenate. Considering both its high specificity and its lack of subtype selectivity (3H)CGP-12177 seems to be a more suitable ligand than ICYP to non-selectively label beta-adrenoceptors in rat brain.
Département de Pharmacologie, Faculté de Médecine de Paris XII, Creteil, France.
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D
Morin
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Zini
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Urien
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Sapena
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JP
Tillement
D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D014316:Tritium
D000319:Adrenergic beta-Antagonists; D007457:Iodine Radioisotopes; D011412:Propanolamines; D014316:Tritium; D012701:Serotonin; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol; C033394:CGP 12177