Dopamine Stimulates K+ Efflux in the Chick Retina via D1 Receptors Independently of Adenylyl Cyclase Activation

Abstract: Dopamine (DA) stimulated K⁺ efflux (assessed as ⁸⁶Rb⁺ efflux) in retinal suspensions of posthatched chicken. This effect was dose dependent (EC₅₀= 22 μM), was mimicked by the D₁-selective antagonist SKF-38393, and reversed by the D₁-selective antagonist SCH-23390, indicating an involvement of D₁ receptors. Analogues of cyclic AMP (CAMP) did not mimic the DA action. Moreover, DA failed to affect cAMP levels, suggesting that adenylyl cyclase (AC) was not involved. In contrast, forskolin (FSK) stimulated both K⁺ efflux and cAMP accumulation in the retina (EC₅₀ of 10 μM for both effects). The FSK-elicited K⁺ efflux was not mimicked by 1,9-dideoxy-FSK (an analogue of FSK that does not activate AC), suggesting that FSK stimulated K⁺ efflux through the activation of AC. Both DA and FSK inhibited Na⁺,K⁺-ATPase activity in the retina. However, the DA-elicited K* efflux was independent of this inhibition, whereas the FSK effect on K⁺ efflux was largely due to the inhibitory action of the diterpene of the ion pump. A possible role of protein kinase C (PKC) in the DA action was explored. The PKC activator 4β-phorbol 12-myristate 13-acetate (4β-PMA) potently (EC₅₀= 4 nM) stimulated K⁺ efflux. This action was not mimicked by the inactive isomer 4α-PMA. When added together, DA and 4β-PMA behaved in an additive manner, suggesting separate mechanisms of action for these two drugs. Moreover, DA failed to stimulate retinal phosphoinositide hydrolysis, a well-known pathway leading to PKC activation. These data suggest that DA acting through D₁ receptors and independently of AC can modulate its target cell excitability in the chick retina by stimulating K⁺ efflux pathways. The mechanism of the DA action remains to be clarified.