Protein kinase C-dependent coupling of alpha(2A/D)-adrenergic receptors to phospholipase D.
To clarify the role of protein kinase C (PKC) in regulating the coupling pathway of alpha(2)-adrenergic receptors, we examined receptor activation of phospholipase D (PLD) in PC12 cells overexpressing alpha(2A/D) receptors, using [(3)H]phosphatidylbutanol formation as an index of PLD activity. In intact PC12/alpha(2A/D) cells, the ability of either epinephrine or the alpha(2)-receptor-selective agonist UK14304 to stimulate PLD was completely dependent on concomitant PKC activation. Pretreatment with the PKC activator phorbol dibutyrate revealed an agonist-stimulated PLD activity which was blocked by the alpha(2)-receptor-selective antagonist rauwolscine and by pertussis toxin treatment. Removal of extracellular calcium or tyrosine kinase inhibition by genistein pretreatment also eliminated the ability of epinephrine to stimulate PLD. These results indicate that alpha(2A/D)-adrenergic receptors couple via pertussis toxin-sensitive G proteins to PLD in a PKC-requiring and tyrosine kinase regulated manner.
Jinsi-Parimoo
A
A
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Deth
R C
RC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D007700:Kinetics; D016716:PC12 Cells; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002273:Carcinogens; D018341:Receptors, Adrenergic, alpha-2; D010566:Virulence Factors, Bordetella; D015240:Phorbol 12,13-Dibutyrate; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; D002118:Calcium; D004837:Epinephrine