Dopamine stimulates K+ efflux in the chick retina via D1 receptors independently of adenylyl cyclase activation.
Dopamine (DA) stimulated K+ efflux (assessed as 86Rb+ efflux) in retinal suspensions of posthatched chicken. This effect was dose dependent (EC50 = 22 microM), was mimicked by the D1-selective agonist 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 microM 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 4 beta-phorbol 12-myristate 13-acetate (4 beta-PMA) potently (EC50 = 4 nM) stimulated K+ efflux. This action was not mimicked by the inactive isomer 4 alpha-PMA. When added together, DA and 4 beta-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Laitinen
J T
JT
Department of Physiology, University of Kuopio, Finland.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002645:Chickens; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D008297:Male; D009712:Nucleotides, Cyclic / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012414:Rubidium Radioisotopes; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D009712:Nucleotides, Cyclic; D017447:Receptors, Dopamine D1; D012414:Rubidium Radioisotopes; D005576:Colforsin; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D004298:Dopamine