Various applications of pAx measurements are discussed based on the hypothesis that drugs and drug antagonists compete for receptors according to the mass law. Examples are given illustrating the use of pAx measurements to identify agonists which act on the same receptors and to compare the receptors of different tissues. Tests of competitive and noncompetitive antagonism are considered in relation to the antagonisms acetylcholine-atropine, histamine-atropine and acetylcholine-cinchonidine. A new measure, pAh, is introduced to express the activity of unsurmountable antagonists.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1959.tb00928.x

Some quantitative uses of drug antagonists

Solubilization of membranes by detergents

Mechanisms of membrane toxicity of hydrocarbons.

Afhnity for Monovalent Cations. 597 Relationship of Enzyme System to ATP. 598 Isolation of Enzyme System from Other Cells with Active Transport of Na+ and K+ 602 Location of Enzyme System in the Cell. 604 Effect of Cardiac Glycosides. 605 Quantitative Relation between Effect of Na+ + K+ on Enzyme System and Active Transport in Intact Cell. 606 Nature of Enzyme System. 607 Relation of (Na + + K+)-Activated Enzyme System to Active Transport of Cations. 6 10 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6’4

/pdf/enzymatic-basis-for-active-transport-of-na-and-k-across-cell-2agxcysijj.pdf

Enzymatic basis for active transport of na+ and k+ across cell membrane.

Some quantitative uses of drug antagonists. 1958.

Leg nerves from the shore crab (Carcinus maenas) contain an adenosine triphosphatase which is located in the submicroscopic particles. The influence of sodium, potassium, magnesium and calcium ions on this enzyme has been investigated.

The presence of magnesium ions is an obligatory requirement for the activity of the enzyme. Sodium ions increase the activity when magnesium ions are present. Potassium ions increase the activity when the system contains both magnesium and sodium ions. Potassium ions in high concentration inhibit that part of the activity which is due to Na+, while the activity due to Mg++ is not affected. Calcium ions inhibit the enzyme under all conditions.

When Mg++ or Mg++ + Na+ are present in the system, the optimum magnesium concentration is equal to the concentration of ATP. If potassium ions are added, the optimum magnesium concentration is doubled. If calcium ions are also added, the optimum magnesium concentration becomes still higher, and it increases with the calcium concentration.

A majority of these observations may be explained by assuming (a) that the substrate most readily attacked by the enzyme is sodium-magnesium-ATP, (b) that potassium ions stimulate the enzyme directly, and (c) that an increase in the concentration of potassium ions leads to a displacement of sodium ions from the substrate and accordingly to an inhibition of the reaction.

If the system contains the four cations in concentrations roughly equal to those in the crab-nerve axoplasm, an increase in the sodium concentration as well as a decrease in the potassium concentration will lead to an intensification of the enzyme activity. This observation, as well as some other characteristics of the system, suggest that the adenosine triphosphatase studied here may be involved in the active extrusion of sodium from the nerve fibre.

The influence of some cations on an adenosine triphosphatase from peripheral nerves.

https://au.dk/fileadmin/www.au.dk/forskning/nobelprisen_i_kemi_1997/biografi/artikel_01.pdf

Further investigations on a Mg++ + Na+-activated adenosintriphosphatase, possibly related to the active, linked transport of Na+ and K+ across the nerve membrane

Preparation from mammallian brain and kidney of the enzyme system involved in active transport of Na+ and K+

The Na-K pump operates by a stepwise change in Na+ versus K+ affinities and a gating reaction governed by the reaction with ATP. The activity is regulated by the intra- as well as the extr...

Jens Chr. Skou

Papers

The influence of some cations on an adenosine triphosphatase from peripheral nerves.

The influence of some cations on an adenosine triphosphatase from peripheral nerves.

Further investigations on a Mg++ + Na+-activated adenosintriphosphatase, possibly related to the active, linked transport of Na+ and K+ across the nerve membrane

Preparation from mammallian brain and kidney of the enzyme system involved in active transport of Na+ and K+

The Na,K-pump