Binding of a catechol derivative of denopamine (T-0509) and N-tert-butylnoradrenaline (Colterol) to beta 1- and beta 2-adrenoceptors.
The affinities for beta-adrenoceptors, the subtype-selectivity and the agonistic effectiveness of T-0509 (a catechol derivative of denopamine) and colterol (N-tert-butylnoradrenaline; Col) were compared with those of other beta-agonists using a binding assay method. Specific binding of [3H]dihydroalprenolol (3H-DHA) to guinea pig left ventricular and lung membranes was saturable, and Scatchard and Hill analyses suggested that 3H-DHA bound to both membranes with a single population of binding sites with no binding site cooperativity. Addition of 5'-guanylylimidodiphosphate (GppNHp, 30 microM) led to a rightward shift of the 3H-DHA binding displacement curves of T-0509 and Col in both membranes, and the degree of shift was similar to that of full agonists such as isoproterenol (Iso), adrenaline (Adr) and noradrenaline (NA). Both T-0509 and Col were thus considered to be full agonists at both beta 1- and beta 2-adrenoceptors, respectively, unlike denopamine and procaterol. T-0509 and Col showed considerably high affinity for both beta 1- and beta 2-adrenoceptors, and T-0509, like denopamine, was as selective for the beta 1-subtype as NA (4.5-fold compared with Iso as a non-selective agonist), whereas Col was more selective for the beta 2-subtype than Adr (4.5-fold compared with Iso).
Kusayama
T
T
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Oka
J
J
Yabana
H
H
Adachi-Akahane
S
S
Nagao
T
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002396:Catechols / Q000378:metabolism*; D004082:Dihydroalprenolol; D004983:Ethanolamines / Q000494:pharmacology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D008771:Nordefrin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D002396:Catechols; D004983:Ethanolamines; D006150:Guanine Nucleotides; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C011595:colterol; D006165:Guanylyl Imidodiphosphate; D004082:Dihydroalprenolol; C025342:RP333; D011433:Propranolol; D008771:Nordefrin; C037293:denopamine