Influence of Histamine on Adenosine Triphosphatase

In all snake venoms hitherto investigated a powerful ATP-ase (ophio-ATP-ase) has been found, which is activated by magnesium, calcium and cobalt ions and inhibited by zinc ions. 1 , 2 Histamine and pyridoxamine act as inhibitors, epinephrine as activator.

The question arose as to whether similar reactions take place in the animal tissues and thus contribute to the understanding of the intimate action of histamine on many organs. Therefore homogenates of different organs were tried on their ability to split ATP. Similar conditions as with ophio-ATP-ase were used (Table I).

Three ATP-ases are known to occur in animal tissues. The ATP-ases from electric tissues of fish 3 and from mammal muscle 4 are activated by magnesium and inhibited by calcium, while the ATP-ase that is inseparable from myosine is influenced by these ions in the opposite way. 5

In the lung, gastric mucosa, adrenal and kidney of guinea pigs, and in the cortex and medulla of adrenals of cattle an ATP-ase is present which is activated by magnesium, calcium and cobaltions. The activation by magnesium is the highest and sometimes reaches values which are 10 times higher than the original ones. 0.00001-molar magnesium chloride still caused a rise in ATP-ase activity. By these reactions this ATP-ase differs from the above-mentioned 3 ATP-ases of animal tissues, but resembles the ophio-ATP-ase. The identity is not complete, since zinc ions accelerate the reaction velocity of the new ATP-ase.

The reaction does not stop completely after the liberation of one molecule of phosphoric acid, but the reaction velocity drops after reaching this point. These and other results lead to the assumption that the second molecule of phosphoric acid is split off by other enzymes. This question needs further elucidation.

The new ATP-ase is affected by histamine and epinephrine in a similar way as is ophio-ATP-ase. The highest degree of inhibition is usually reached in the presence of a magnesium concentration that is below the optimum. Under certain conditions calcium exactly counterbalances the influence of histamine.