The specific binding of broxaterol, a new beta 2-selective agonist, to beta-adrenoceptors

The specific binding of broxaterol, a potent new orally active antiasthmatic drug, to beta 1- and beta 2-adrenoceptors was characterized by receptor binding studies with rat heart and lung membrane preparations. Broxaterol showed high affinity and selectivity for the beta 2-component of [3H]dihydroalprenolol binding in both lung (58% beta 2-sites, Ki = 130 nM) and heart membranes (19% beta 2-sites, Ki = 98 nM), whereas the binding to the beta 1-component was at lower affinity (42% beta 1-sites, Ki = 4100 nM in the lung and 81% beta 1-sites, Ki = 3460 mM in the heart). The influence of temperature changes on the binding properties of broxaterol towards beta-adrenoceptors was also investigated. A marked increase in the affinity of broxaterol for lung beta-receptors was observed on lowering the assay temperature, whereas the affinity for heart beta-receptors was little affected by temperature changes. Thermodynamic analysis of the binding data showed that the binding of broxaterol as well as isoproterenol to lung beta-receptors was associated with a large decrease in enthalpy, which correlates well with the full agonistic properties of this compound at beta 2-receptors.