title: Binding of beta-adrenoceptor antagonists to rat and rabbit lung: special reference to levobunolol.
abstract: Binding of 3H-dihydroalprenolol (3H-DHA) to beta-adrenoceptors in homogenates from rat and rabbit lung was homogeneous and of high affinity (KD = 0.6 and 1.1 nmol/l at 20 degrees C; 1.1 and 2.2 nmol/l at 37 degrees C). The beta 1-selective antagonists betaxolol, metoprolol, bevantolol and acebutolol displaced 3H-DHA in a biphasic manner. From these data, the beta-adrenoceptor subtype distribution in rat lung homogenates was estimated to be 80% beta 2 (at 20 and 37 degrees C) as compared to 25% beta 2 in rabbit lung homogenates. In general, binding of beta-adrenoceptor antagonists (selective and nonselective) was slightly (less than 2 X) weaker in rabbit than in rat lung homogenates. In rat lung, binding of cardioselective beta-blockers to beta 1-receptors seemed to be more temperature-sensitive than binding to beta 2-receptors or binding of nonselective beta-blockers. Levobunolol, a potent non-cardioselective beta-blocker in pharmacological experiments, displaced 3H-DHA in a homogeneous manner (indicative of non-selectivity). In rat lung homogenates KD values were 0.8 nmol/l at 20 degrees C and 2.1 nmol/l at 37 degrees C. Similar values were found for the metabolites dihydrolevobunolol and hydroxylevobunolol. Surprisingly, d-bunolol, the dextrarotatory enantiomer of bunolol, showed a biphasic displacement curve, the fraction of high affinity sites being 83% in rat lung homogenates and 23% in rabbit lung. This ratio of sites is expected for a beta 2-adrenoceptor preferring ligand. High affinity binding (i.e. supposedly binding to beta 2-receptors) was about 50 times weaker than binding of levobunolol, in agreement with known stereospecificity of beta-adrenoceptor binding.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004082:Dihydroalprenolol / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D002040:Levobunolol / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013237:Stereoisomerism; D013696:Temperature
chemical_list: D000319:Adrenergic beta-Antagonists; D004082:Dihydroalprenolol; D002040:Levobunolol