Protein Kinase C-Dependent Coupling of α2A/D-Adrenergic Receptors to Phospholipase D

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Abstract
To clarify the role of protein kinase C (PKC) in regulating the coupling pathway of α2-adrenergic receptors, we examined receptor activation of phospholipase D (PLD) in PC12 cells overexpressing α2A/D receptors, using [3H]phosphatidylbutanol formation as an index of PLD activity. In intact PC12/α2A/D cells, the ability of either epinephrine or the α2-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 α2-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 α2A/D-adrenergic receptors couple via pertussis toxin-sensitive G proteins to PLD in a PKC-requiring and tyrosine kinase regulated manner.