Abstract

Within the dopamine receptor family, the D3 dopamine receptor's function remains inadequately described. The D3 receptor has been shown to couple to inhibition of adenylyl cyclase, stimulation of mitogenesis, and regulation of K+ and Ca2+ currents, all in a pertussis toxin (PTX)-sensitive manner. Here we report D3 receptor activation of the phospholipase D (PLD) enzyme in HEK 293 cells heterologously expressing the human D3 receptor. Activation by agonist is dose dependent and displays the pharmacology expected of the D3 receptor. The D3 receptor specific antagonists AJ-76 and U99194A ablated the increase in activity by the preferring D3 agonist (+) 7-OH DPAT. In addition, the D3 receptor-mediated activation of PLD is not mediated by G-proteins of the Gi/Go family, as pretreatment with PTX had no effect. PLD activation is a novel finding for the D3 receptor, and is the first example of an effector system where D3 signals without Gi/Go protein intermediates.

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