564 DYNAMIC ASPECTS — PERMEABILITY AND TRANSPORT 
DISCUSSION 
Chairman: HALVOR CHRISTENSEN 
L. RosENBERG: I would appreciate a little further clarification of this concept of exchange diffusion 
from either Dr. CHRISTENSEN or Dr. HEINz and perhaps a little further discussion of the mechanisms 
of the loading experiments that I think each of you reported. 
Hernz: If you preload these cells with unlabeled glycine, and then expose them to labeled 
glycine, the influx of the labeled glycine is greatly increased as compared to the control. I 
think this phenomenon is related to those, described later under other names, such as “induced 
uphill transport by counterflow”, by Dr. ROSENBERG AND Dr. WILBRANDT, by Park ef al., and by 
others. 
CHRISTENSEN: Perhaps I might offer this word of explanation. If you let a given cell take up, 
let us say, leucine to a steady state, perhaps there will be three times as much inside as there is 
outside. But if you take cells that have already been loaded with leucine to quite a high level by 
exposing them to a high environmental leucine concentration, and then put on the outside !C- 
labeled leucine, you will have in the course of one minute a rise in the level of !4C-label inside to 
approximately twelve times the outside level. Then leucine-“C will eventually return to the 3 : 1 
distribution, corresponding to a constant specific activity for an essentially unchanged load of 
leucine. This behavior means, while #*C-leucine is moving out with the gradient, that C-leucine 
is driven into the cell against the gradient. The transport site does not differentiate between these 
two forms. So far as site is concerned, nothing is happening, but so far as the observer is concerned, 
uphill transport is being produced by counterflow. In the case of two different amino acids the 
behavior may seem still more dramatic, but the site still considers them the same, except perhaps 
for slight affinity differences. 
LajTHa: I would like to add here that there may be some similarity between transport mecha- 
nisms in ascites cells and brain. I think exchange diffusion also occurs in brain. As with ascites in 
the experiments discussed just now, preloading the brain increases cerebral exchange. That is, 
the uptake of labeled amino acid from the plasma by the brain is greater in the brains in 
which amino acid levels were increased by intracerebral administration. However, there seems to 
be some specificity in that preloading the brain with leucine increases leucine exchange and not 
lysine exchange and, in turn, preloading with lysine increases lysine exchange more than leucine 
exchange. Dr. GuroFF discussed at this meeting, and we did several times at other places, that al- 
though net uptake in brain is restricted, a rapid exchange of most amino acids between brain and 
plasma can be shown. I find exchange diffusion again the most probable explanation for this 
phenomenon. 
E. Roperts: I might just add a word of caution about such work with brain. When one studies 
exchanges in slices, it should be kept in mind that exchanges observed may be taking place in 
several different cell types. There seems to be an inference in the discussion that the exchange is 
occurring in a uniform preparation. But since there are several cell types, there may be uptake 
into one and exchange in another. I think that for the moment this presents such a complex 
problem that it is difficult to see how one can analogize those results with those obtained using 
single cell types such as bacteria or ascites tumor cells. 
LajTHa: Of course, Dr. ROBERTS is correct in reminding us of the great complexity of the brain 
and we should be aware of the many possible explanations and not oversimplify the picture. At 
present, however, at least to me, of all such possible explanations of the above discussed pheno- 
mena, including that uptake into one cell alters exchange in another, that of exchange diffusion is 
the most attractive and most plausible. 
CHRISTENSEN: I wanted to take the opportunity to comment on the paper of Dr. Heinz. At the last 
Federation meeting (April 1961), Dr. OXENDER AND Dr. Royerreported further on the identification 
of the site of action of pyridoxal and pyridoxal phosphate, showing that it does work on a mediated 
process outwarvd, a mediated efflux. This was established by showing that the process concerned is 
subject to saturation, to competition, and also serves for exchange. With these three properties, 
diffusion is ruled out as the efflux process being slowed. 
We are coming to question, now, whether there really is very much migration by diffusion into 
or out of normal cells. Instead, mediations may be entirely responsible. I should like to call this 
