Three binding sites of 125I-iodocyanopindolol, i.e. beta 1, beta 2-adrenergic and 5HT1B-serotonergic receptors in rat brain determined by the displacement and Scatchard analysis.
The selectivity of binding of 125I-iodocyanopindolol (125I-ICYP) to beta 1-, beta 2-adrenergic and 5HT1B-serotonergic receptors were analysed using both the Scatchard and displacement methods. When the binding of 125I-ICYP to the rat brain membrane was examined by means of the displacement analysis with l-metoprolol, triphasic displacement curves were observed. Analyses carried out on the basis of the displacement of 125I-ICYP by beta-selective antagonists, alpha-adrenergic agonists and antagonists, and serotonergic agonists and antagonists indicated the correspondence of the super high, high- and low-affinity sites of 125I-ICYP binding to beta 2-, beta 1-adrenergic and 5HT1B-receptors, respectively. By contrast, the Scatchard analysis revealed the biphasic character of the 125I-ICYP binding and the complete inhibition of the binding to high- and low-affinity sites by l-metoprolol (30 microM) and 5-hydroxytryptamine (5HT, 10 microM), respectively, suggesting the correspondence of the high- and low-affinity sites to beta-adrenergic and 5HT1B-receptors. Thus, regarding the determination of the selectivity of binding of a radioligand, the displacement analysis is more informative than the Scatchard analysis. In the case of 125I-ICYP the separation of beta 1- and beta 2-adrenergic receptors becomes feasible only with the displacement method.
Tsuchihashi
H
H
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Nagatomo
T
T
Imai
S
S
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007700:Kinetics; D008433:Mathematics; D008566:Membranes / Q000378:metabolism; D008790:Metoprolol / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D012701:Serotonin; D020120:Iodocyanopindolol; D011433:Propranolol; D010869:Pindolol; D008790:Metoprolol