Pharmacological characteristics of beta-adrenoceptor binding sites in intact and sympathectomized rat spleen.
[3H]-(--)-Dihydroalprenolol ([3H]-DHA) binds to rat spleen membranes with a dissociation equilibrium constant (KD) of about 0.7 nM and a maximal number of binding sites of 272 fmoles x mg protein-1. Approximately 90% of the sites labelled by 1 nM [3H]-DHA possess classical properties of beta-adrenoceptors. The labelled ligand is stereospecifically displaced by the isomers of propranolol and the order of potency of agonists is: isoprenaline greater than adrenaline greater than noradrenaline. Highly selective beta 1 antagonists such as practolol and atenolol displaced [3H]-DHA from spleen membranes in a biphasic manner indicating the co-existence of beta 1 and beta 2 sites (30--35% beta 1; 65--70% beta 2) in this tissue. Support for this classification was provided by the binding of the beta 2 agonist procaterol to spleen membranes. This drug possessed high affinity only for those sites that have low affinity for the beta 1 selective agents. Chemical sympathectomy induced by chronic 6-hydroxydopamine administration did not alter the number or the pharmacological properties of beta-adrenoceptor binding sites. The results suggest that both beta 1 and beta 2 adrenoceptors are probably postsynaptic in spleen.
D000526:Alprenolol; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D004082:Dihydroalprenolol; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013154:Spleen / Q000294:innervation / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects
D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D000526:Alprenolol; D009638:Norepinephrine