Stimulation of Monovalent Cation Active Transport by Low Concentrations of Cardiac Glycosides

Abstract

A B S T R A C T The stimulatory effect of low concentrations ofouabain on the Na-K pump in isolated guinea pig left atria was studied in vitro by assessing active transport of the K+ analog Rb+. Active transport of Rb+ was stimulated 20+8% (SEM, P < 0.05) above control values by 3 nM ouabain, but was inhibited by concentrations >10 nM. Preincubation with the f-adrenergic antagonist propranolol (1 ,uM) completely blocked stimulation of active transport of Rb+ by 3 nM ouabain. Norepinephrine, 10 nM, increased Rb+ active transport 29±10% (P < 0.02) above control values. The /8-adrenergic agonist 1-isoproterenol, 10 nM, increased active transport of Rb+ by 33±10% (P < 0.01) above control levels. This stimulatory effect was abolished if tissues were first exposed to propranolol. Tyramine (0.1 ,uM), a stimulator of endogenous catecholamine release, increased active transport of Rb+ 26±12% (P < 0.05) above control values. Rb+ active transport was not significantly changed when left atrial tissues were incubated with a-adrenergic agonists or antagonists. Ouabain stimulation of Rb+ active transport was prevented by in vivo depletion of myocardial endogenous catecholamines by either reserpine or 6-hydroxydopamine. These findings indicated that in myocardial tissue, Na-K pump stimulation by low concentrations of ouabain is mediated at least in part through j8-adrenergic effects of endogenous catecholamines.

Endogenous Sodium Pump Inhibitors and Blood Pressure Regulation: An Update on Recent Progress

“…No such stimulatory effect was observed in vascular rings pretreated with phentolamine (24). Similar stimulation due to norepinephrine release caused by nanomolar doses of digitalis was observed in isolated guinea pig hearts (109).…”

Enhancement of calcium current during digitalis inotrophy in mammalian heart: positive feed‐back regulation by intracellular calcium?

“…Since these effects of ouabain are reminiscent of changes in Ii and contractile force produced by ,-adrenergic compounds (see for example, Reuter, 1974), it is important to consider indirect effects due to ouabain-evoked release of catecholamines from sympathetic nerve endings (e.g. Hougen et al 1981). To rule out this possibility, the experiment in Fig.…”

Quantification of the Na, K‐Pumps in Mammalian Skeletal Muscle

“…It has been reported, that very low concentrations of ouabain activate the Na,K-ATPase or K-dependent phosphatase activity (Pitts & Askari, 1971). However, this has never been verified with purified preparations and the stimulation seen in intact tissues or homogenates is probably mediated by catecholamines released from neural tissue present (Hougen et al, 1981). Thus, the stimulation of some pumps by catecholamines may overshadow the inhibition by ouabain of others (Hansen, 1984).…”