Effects of Na⁺ and K⁺ on the uptake of metaraminol by rabbit ventricular slices

Abstract

4. The inhibitory effects on transport of either a marked reduction in the concentration of Na+ or of omission of K+ were rapidly reversible on exposure of slices to Krebs solution. 5. The inhibitory effect of ouabain on [3H]-metaraminol transport was markedly time dependent, being significantly increased by preincubation with ouabain. The inhibitory action of ouabain was not affected, however, by the Na+ concentration present during preincubation. 6. An inwardly directed Na+ gradient did not increase [3H]-metaraminol transport in slices in which Na+ pumiping had been prevented by 1O-5M ouabain, 40 C, omission of K+ or by metabolic inhibition. 7. These findings provide additional evidence that the Na+ and K+ activated adenosine triphosphatase may participate in the transport of metaraminol and related amines. In the absence of Na+ pumping, induced Na+ gradients were unable to produce transport of amine as would be predicted by the co-transport model proposed by . IntroductionTissues accumulate noradrenaline and structurally related compounds such as metaraminol, by a process which is temperature dependent, requires energy, is Na+ and K+ dependent and is inhibited by ouabain (Dengler, Michaelson, Spiegel &

Uptake kinetics and ion requirements for extraneuronal uptake of noradrenaline by arterial smooth muscle and collagen

“…A particular feature of these Na+-coupled uptakes is the high specificity for sodium; no other ion tested can fully replace Na+ (Schultz & Curran, 1970). This high specificity applies to the neuronal uptake of noradrenaline where lithium, tris, choline, rubidium, caesium and potassium are all ineffective substitutes (Horst et al, 1968;Bogdanski & Brodie, 1969;Paton, 1971). Lithium has been particularly studied and only one study on synaptosomes shows that it can substitute to a small extent for Na+ (Baldessarini & Yorke, 1970).…”

Mechanism of efflux of noradrenaline from adrenergic nerves in rabbit atria

“…It is possible that this effect is related to the inhibition of coupled Na+/K+ pumping produced by such procedures. Inhibition of the Na pump results in an increase in the intracellular Na+ concentration and, according, to the Na+-gradient hypothesis, would be expected to increase efflux of solute by either reducing the Km or increasing the Vmax for efflux (Schultz & Curran, 1970 (Paton, 1971 ;White & Paton, 1972). By contrast, effiux of amine was clearly not inhibited by inhibition of the Na+/K+ activated ATPase or by depletion of cellular ATP.…”

“…(e) Inhibition of Na pumping Both ouabain (Dengler, Michaelson, Spiegel & Titus, 1962) and omissicn of K+ from the external medium (Gillis & Paton, 1967) adrenaline and related amines by adrenergic nerves, possibly as a result of inhibition of the Na+-K+ activated ATPase (Bogdanski & Brodie, 1969;Paton, 1971). According to the Na+-gradient hypothesis, inhibition of the net uptake of amine thus produced should result primarily from an increase in efflux (Schultz & Curran, 1970).…”

“…However, changes in the external concentration of Na+ altered the Vma, for transport of metaraminol (Sugrue & Shore, 1969) and noradrenaline (White & Paton, 1972) but did not alter the Km. In addition, the inwardly-directed Na+ concentration gradients did not stimulate or restore uptake in metabolically-inhibited preparations (White & Keen, 1970;Paton, 1971). Since these findings were not predicted by the model of Bogdanski & Brodie, alternative models were considered by White & Paton (1972).…”

Metabolic Requirements for the Uptake of Noradrenaline by Isolated Atria and Vas Deferens of the Rabbit

“…Much evidence has accumulated that sympathetic postganglionic neurones concentrate noradrenaline and certain structurally-related com pounds such as metaraminol, from the external medium [11,13] by a membrane transport process which is temperature-sensitive [4,7], in hibited by ouabain [4,18] and is Na+-and K+-dependent [1,6,[16][17][18]. In addition, uptake of the amine requires energy [16,22].…”