title: (+/-)[125Iodo] cyanopindolol, a new ligand for beta-adrenoceptors: identification and quantitation of subclasses of beta-adrenoceptors in guinea pig.
abstract: (+/-)[125Iodo] cyanopindolol (ICYP) is a radioligand which binds with an extraordinarily high affinity and specificity to beta-adrenoceptors. In contrast to (+/-) [125Ido]-hydroxybenzylpindolol (IHYP), the new ligand has neither affinity to alpha-nor to 5-HT-receptors. The dissociation constants of ICYP for beta- adrenoceptors in various tissues range from 27 to 40 pM, thereby exceeding the affinity of IHYP by a factor of approximately 3. ICYP does not discriminate between beta 1- and beta 2-adrenoceptors. Therefore, the densities of the two receptor subtypes can be determined from competition curves of ICYP by drugs previously found to show in vitro selectivity for beta 1-adrenoceptors. The guinea pig left ventricle contains only beta 1-adrenoceptors, whereas in a lung tissue, the ratio of beta 1-to beta 2-adrenoceptors is 1 to 4. The calculated affinities of five beta 1-selective antagonists for beta 1-adrenoceptors were nearly identical in the ventricle and the lung. Kinetic studies of ICYP binding to guinea pig lung membranes indicated that the dissociation reaction consists of two components, a fast process (t 1/2 = 9 min) and a slower process (t 1/2 = 8.8 h). A mathematical treatment revealed two possibilities of interpretation: 1. Two forms of the receptor exist which are interconvertible. 2. The (+)- and (-)- enantiomers of ICYP dissociate with different rate constants. The low dissociation constant of ICYP in combination with its high specific radioactivity (2175 Ci mmole -1) allows binding studies to be carried out with small protein and ligand concentrations, e.g. 3 microgram protein per assay in guinea pig lung membranes.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003201:Computers; D006168:Guinea Pigs; D020120:Iodocyanopindolol; D007700:Kinetics; D008024:Ligands; D008066:Lipolysis / Q000187:drug effects; D008168:Lung / Q000378:metabolism*; D008297:Male; D008956:Models, Chemical; D009206:Myocardium / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; D008024:Ligands; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C011878:iodohydroxybenzylpindolol; D020120:Iodocyanopindolol; D010869:Pindolol