Ecf - every reason for presence of interacting multiple homeostatic control mechanisms

M. R. Wilkins in his article 1 on the existence of an endogenous digi- talis in animals asks the question 'why should mammalian cells bear a receptor for a vegetable extract'. He places little emphasis on the analogy with the opiates, another vegetable extract, and the naturally occurring endorphins. On the basis of the evidence cited, Wilkins takes the view that the existence of such an agent is in serious doubt. Indeed, he ques- tions whether there is a need for a ouabain-like substance (OLS) with natriuretic properties given the recent discovery of the atrial natriuretic peptides. We could extend the argument and indeed, question the need for the atrial natriuretic peptides given the renin-angiotensin-aldoster- one system in the control of Na + excretion. In view of the vital importance of the Na + ion in the control of the extracellular fluid volume, there is clearly every reason for the pre- sence of interacting multiple homeostatic control mechanisms. The delay in the isolation and structuring of the postulated OLS in particular from human plasma, is, in our view, primarily because of technical difficulties in the isolation of an unknown material. Some of the problems have been discussed in detail elsewhere 2. The atrial peptides were purified and sequenced from atrial tissue 3 where they are present in large amounts and furthermore the speed with which the work was accomplished was greatly aided by the well established protein/ peptide technology. One could ask how long it would have taken to purify the atrial peptides from human plasma where they are present in extremely low amounts (about 10pgm1-1 plasma; Sag- nella, G. A., unpublished observa- tions). Although Wilkins men- tions that the OLS may originate from the hypothalamus he has not cited more recent work on the identification and partial purifica- tion of a OLS from neuronal and hypothalamic extracts 4,5. Using modern isolation procedures 393 these groups have found a high affinity Na+/K+-transporting ATPase inhibitor. Hauper