Abstract
Within the dopamine receptor family, the D 3 dopamine receptor's function remains inadequately described. The D 3 receptor has been shown to couple to inhibition of adenylyl cyclase, stimulation of mitogenesis, and regulation of K + and Ca 2+ currents, all in a pertussis toxin (PTX)-sensitive manner. Here we report D 3 receptor activation of the phospholipase D (PLD) enzyme in HEK 293 cells heterologously expressing the human D 3 receptor. Activation by agonist is dose dependent and displays the pharmacology expected of the D 3 receptor. The D 3 receptor specific antagonists AJ-76 and U99194A ablated the increase in activity by the preferring D 3 agonist (+) 7-OH DPAT. In addition, the D 3 receptor-mediated activation of PLD is not mediated by G-proteins of the G i/G o family, as pretreatment with PTX had no effect. PLD activation is a novel finding for the D 3 receptor, and is the first example of an effector system where D 3 signals without G i/G o protein intermediates.
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