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>adrenaline >noradrenaline. Highly selective beta1 antagonists such as practolol and atenolol displaced [3H]-DHA from spleen membranes in a biphasic manner indicating the co-existence of beta1 and beta2 sites (30-35% beta1; 65-70% beta2) in this tissue. Support for this classification was provided by the binding of the beta2 agonist procaterol to spleen membranes. This drug possessed high affinity only for those sites that have low affinity for the beta1, 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 beta1 and beta2 adrenoceptors are probably postsynaptic in spleen. © 1979 Springer-Verlag.