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.
Zambon Research S.P.A., Bresso, Milan, Italy.
R
R
Sala
E
E
Moriggi
D
D
Della Bella
A
A
Carenzi
D000318:Adrenergic beta-Agonists / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004082:Dihydroalprenolol / Q000494:pharmacology; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013816:Thermodynamics
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007555:Isoxazoles; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D011433:Propranolol; C045916:broxaterol