cAMP stimulates the Na+-K+ pump in frog retinal pigment epithelium

Adenosine 3', 5'-cyclic monophosphate (cAMP) induced increases in active Na+ secretion and K+ absorption that were blocked by apical ouabain (10(-4) M), suggesting stimulation of the Na+-K+ pump. cAMP also produced rapid membrane voltage and resistance changes that could be divided chronologically into three phases. In phase 1, the basolateral membrane depolarized at a faster rate than the apical membrane, probably as a result of an increase in basolateral membrane conductance. In phase 2, the apical membrane repolarized toward control faster than the basal membrane, whereas in phase 3 the basolateral membrane repolarized faster than the apical membrane. Apical ouabain completely inhibited the cAMP-induced repolarization of the apical membrane during phase 2. Thus the stimulation of the Na+-K+ pump occurs within minutes of cAMP elevation. Na+ removal from the basal side did not block the cAMP-induced voltage changes, indicating that the initial conductance increase is not due to Na+. In contrast, Na+ removal from the apical bath inhibited all phases of the cAMP response. This suggests that apical membrane Na+-dependent transport mechanisms mediate the stimulation of the Na+-K+ pump. cAMP also caused a significant drop in intracellular K+ activity (approximately 5 mM) that preceded phase 2. This drop could stimulate the Na+-K+ pump, as suggested by previous experiments.