Selectivity of Dobutamine for Adrenergic Receptor Subtypes: IN VITRO ANALYSIS BY RADIOLIGAND BINDING

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Abstract

The cardiovascular responses elicited by dobutamine are distinctly different from those produced by other adrenergic or dopaminergic agonists. To test the hypothesis that dobutamine could have differential affinities for adrenergic receptor subtypes, and that such subtype selectivity could be related to its relatively unique pharmacologic properties, we assessed the ability of dobutamine to displace adrenergic radioligands from membrane receptors in a number of tissues of previously characterized adrenergic receptor subtype. For beta adrenergic receptors identified by (−) [3H]dihydroalprenolol (DHA), dobutamine had significantly greater affinity for the β1 subtype (KD = 2.5 μM in rat heart and 2.6 μM in turkey erythrocyte) than for the β2 subtype (KD = 14.8 μM in frog heart and 25.4 μM in rat lung) (P < 0.001). For alpha adrenergic receptors, dobutamine had markedly greater affinity for the α1-subtype identified by [3H]prazosin (KD = 0.09 μM in rat heart and 0.14 μM in rabbit uterus) than for the α2-subtype identified by [3H]dihydroergocryptine (DHE) (KD = 9.3 μM in human platelet) or by [3H]yohimbine (KD = 5.7 μM in rabbit uterus) (P < 0.001).

Authors

R. Sanders Williams, Timothy Bishop