Abstract
Field, Martin and Field 1 , 2 , 3 have shown that the stimulation or inhibition of yeast respiration by 2-4 dinitrophenol (DNP) and several related compounds depends upon the concentration of the undissociated form. Since this finding appears to have important physiological and pharmacological implications, we have undertaken an investigation of the action of DNP on excised rabbit striated muscle (diaphragm) to see whether the undissociated form is the active agent in stimulation of oxygen consumption of a mammalian tissue as well as of yeast.
Rabbits were killed by a blow on the back of the neck. The diaphragm was rapidly excised, and strips of proper thickness (c. f. Warburg 4 ) were placed in Ringer's solution containing 0.2% glucose and buffered at the desired pH with M/150 phosphate. Respiration was measured by the Warburg manometric method 4 at 37° ± 0.02°C. in an atmosphere of oxygen. The respiration of each piece of tissue was followed for 30 minutes before addition of DNP from the vessel sidearms, to obtain a preliminary control period in each case. In addition to these individual controls in at least one case in every run (6 to 13 vessels), Ringer's-glucose was added from the sidearms instead of DNP to determine the rate of decrease of oxygen consumption with time under the conditions of these experiments over a longer period.
Calculations of percentage stimulation (Table I) were based on the assumption that had no DNP been added the rate of decrease of oxygen consumption after the initial control period would have been the same as that observed in the longer control experiments. Controls showed this assumption valid within ±5%. Accordingly, no change in oxygen consumption was considered significant unless it exceeded 10%.
If undissociated DNP is the active agent in the stimulation or inhibition of tissue respiration by this substance, one would expect to find the optimum total concentration to be a function of pH, while the optimum concentration in terms of the undissociated form should be quite constant.
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