VOL. 4 (1950) METABOLISM OF NUCLEATED RED CELLS 277 



in vitro is essentially with the metabolic response to stimulation in vivo. This is further 

 borne out by observations of Brock, Druckerey and Herken^ who confirmed the 

 findings of Deutsch and Raper. They calculated the metabolic turnover of the whole 

 salivary gland from the values obtained in vitro on slices and found after stimulation 

 values which agreed well with values obtained by Barcroft and Peper^ on the salivary 

 gland stimulated in vivo by chorda tympani. They found, furthermore, that the "stimu- 

 lation metabolism", as they call the metabolic response of tissue slices to stimulants, 

 depends on the ionic equilibrium in the Ringer solution in which the slices are suspended. 

 Complete removal of the Ca from the Ringer suppresses completely the stimulation 

 response, which can be restored by the subsequent addition of Ca. The removal of K ions 

 does not suppress the first response but prevents the recovery. The ionic equilibrium 

 in the medium is essential for the structural integrity of the cell or at least its surface 

 membrane. It is therefore clear that the stimulation response requires the integrity 

 of the cell structure and cannot be a consequence of injury and structural disintegration. 



The stimulation metabolism shows two significant features as compared with the 

 basic or rest metabolism: i. the latter has a R.Q. below i while the excess respiration 

 after stimulation has a R.Q. of i, indicating a pure carbohydrate metabolism; 2. the 

 increase in Og uptake is always paradoxically accompanied by a production of free 

 acids, of which at least half was shown by Deutsch and Raper to be lactic acid^. 

 Brock, Druckerey, and Herken* have shown that this production of acid does not 

 occur when K ions are removed from the surrounding medium, although the increase 

 in respiration appears unchanged in size after the first stimulus. 



The characteristic metabolism response to hormonal or pharmacological stimuli is 

 by no means a peculiarity of glandular tissues. The increased respiration of the sea 

 urchin egg after fertilization shows all the characteristic properties of the stimulation 

 metabolism of glands^. The production of free acid in this case was found by Runnstrom, 

 although the nature of the acid was not definitely established. As in glands there is also 

 a marked difference in the sensitivity towards HCN between the respiration of the 

 unfertilized and that of the fertilized egg. And according to Brock ei al. a hormonal 

 extract of the anterior pituitary which influences the division of the egg provokes the 

 same characteristic metabolic response in it as fertilization. This cannot be obtained 

 with extracts which do not influence the cleavage of the eg^. 



Finally a similar metabolic response was observed in 1937 by Gottdenker and 

 Marchi^ on mammalian heart lung preparations. They found that adrenaline, which is 

 a heart stimulant, increased the O2 uptake of these preparations and at the same time 

 provoked an intensive lactic acid production. 



The fact that the increased respiration in stimulated tissue slices goes on at the 

 expense of carbohydrates and is accompanied by formation of lactic acid only under 

 physiological conditions of the medium suggests a certain interpretation of the mecha- 

 nism of this metabolic phenomenon. The anaerobic glycolysis of the glands is completely 

 suppressed by the basic respiration due to the Pasteur effect. Any factor leading to 

 a deteriorization of the structural integrity of the cell tends to provoke an aerobic 

 glycolysis. This is the case for instance with liver or brain slices when K is removed 

 from the medium. The aerobic glycolysis accompanying the stimulation response differs 

 in this respect fundamentally in being dependent on the presence of K ions in the me- 

 dium and is suppressed completely after their elimination. This indicates clearly that 

 aerobic glycolysis of stimulation is not due to structural damage or increase of per- 

 References p. 2g2. 



