Rapid and reversible uncoupling of the hepatic alpha 1-adrenergic receptor and guanine-nucleotide-binding protein by phorbol 12,13-dibutyrate.
Phorbol 12,13-dibutyrate (PDBU), 1 microgram/ml for 2 min, abolished alpha 1-adrenergic receptor (AR)-mediated signal transduction in rat hepatocytes and converted 100% of alpha 1-ARs to a low-affinity state, similar to effects of a non-hydrolyzable GTP analog. Reversal of PDBU inhibition restored high-affinity alpha 1-ARs towards control values. The rapid uncoupling of the alpha 1-AR and guanine-nucleotide-binding protein by PDBU, and reversibility associated with reactivation of alpha 1-adrenergic signaling, identify this as an important inhibitory locus for PDBU.
Department of Pharmacology, University of South Carolina School of Medicine, Columbia 29208.
J F
JF
Beeler
R H
RH
Cooper
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014475:Uncoupling Agents / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D014475:Uncoupling Agents; D015240:Phorbol 12,13-Dibutyrate; D019204:GTP-Binding Proteins; D009638:Norepinephrine; D011224:Prazosin