Action of D3 receptors on ion channels

Like D2 receptors, when D3 receptors are transfected in heterologous systems, they are able to stimulate Na+/H+ exchange in the cells producing an acidification of the culture medium. This effect is due to the activation of the amiloride-sensitive Na+/H+ antiporter and is dependent on a Gi/Go protein activation and partly on the inhibition of cAMP production (Chio et al., 1994a Vanhauwe et al., 1999). However, the D3 receptor stimulation appeared to be less efficiently than that of D2 receptor on this response (Chio et al., 1994a Vanhauwe et al., 1999). 

D3 receptors have coupling mechanisms qualitatively similar to D2 receptors, although this coupling seems to be less efficient. They may have a preferential ability to inhibit ACV with which they are coexpressed in the ventral striatum, and they have the possibility to interact directly with SH3 domain containing proteins, although the physiological role of this interaction remains to be established. 

As observed with the other D2-like receptors, the D4 receptors mediate additional signaling events that are independent of the changes in cAMP levels. Some of these intracellular signals can be transduced by the Gpy complex. This is probably the case in HEK 293 transfected with a Gpy-sensitive adenylyl cyclase (ACII), in which activation of D4 receptor paradoxically produced a stimulation of cAMP production (Watts and Neve, 

In Xenopus oocytes, GIRK1 channels which can be stimulated by G(3y subunits, were opened following the activation of D4 receptor (Werner et al., 1996 Pillai et al., 

Ca2+ channels, agonists produce transient increases in intracellular Ca2+ levels that probably result from the activation of the phosphoinositide hydrolysis and Ca2+ mobilization from intracellular stores (Kazmi et al., 2000). 

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