The effect of high concentrations of alpha 2-adrenoceptor antagonists on the lipolytic responsiveness of isolated human adipocytes.
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.
van de Venter
M
M
Department of Biochemistry, University of Port Elizabeth, South Africa.
Litthauer
D
D
Oelofsen
W
W
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; C058525:2-methoxyidazoxan; D007545:Isoproterenol; C033394:CGP 12177; D009638:Norepinephrine; D019329:Idazoxan