1. Non-specific effects of alpha 2-adrenergic antagonists on human adipocyte lipolysis are reported, and revealed that yohimbine and RX-821002 (10(-4) M) decreased the maximum lipolytic response and increased the ED50 towards norepinephrine and isoproterenol. 2. These effects were not mediated by adenosine receptors, alpha 2-adrenoceptors or Gi proteins. 3. Whereas alpha 2-antagonists, even as low as 10(-8) M, decreased the binding affinity of [3H]CGP-12177, levels as high as 10(-3) M of these antagonists were needed to cause 10-20% displacement of the beta-selective antagonist. 4. We propose that the antilipolytic effects of alpha 2-antagonists can only partly be explained by non-specific binding to beta-adrenoceptors, and that some other mechanism is also involved.
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