The two members of the D1 -like receptor family (D1 and D5) share a high degree of structural homology and pharmacological similarity. In all the recombinant cell lines expressing these subtypes tested to date, the D1 and D5 receptors stimulate cAMP formation in response to an agonist, an effect which involves the activation of the G proteins of the Gs family. The D5 receptor has been shown to activate adenylate cyclase activity independent of agonist (constitutive activation) and the D1-like receptors cloned from Xenopus laevi and from chicken also mediate dopamine stimulation of adenylate cyclase (Tiberi et al. 1994; Sugamori et al. 1994; Liu etal. 1992). The D1-like receptors were also found to couple to several other pathways in different cell lines. These include changes in the intracellular Ca2+ concentrations, modulation ofNa+/H+ exchanger activity, and modulation ofK+ currents (Frail etal. 1993; Undie etal. 1994; Felder etal. 1993; Laitinen 1993; Pedersen etal. 1994). However, the direct involvement of Gs proteins in these effects is not clear. They may rather involve activation of protein kinases such as protein kinase A or activation of phospholipase C (Frail et al. 1993). Some of the results observed on the intracellular Ca2+ and phospholipase C activation were controversial. For example, when expressed in HEK 293 cells, the human as well as the goldfish D1 receptor increased intracellular Ca2+ (Undie et al. 1994). However, in baby hamster kidney cells, neither D1, nor D5 receptor causes any change in intracellular Ca2+ levels (Hayes et al. 1992). These discrepancies may arise from the difference between the systems in which the receptors were expressed.
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