By G. Alan Robison
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We continue to favor the hypothesis that the receptor is a part of the adenyl cyclase system itself, if only because this seems to be the simplest hypothesis which is consistent with the available facts. Simplicity is not necessarily a virtue in and of itself, but the assumption of a separate receptor system, capable of influencing not only adenyl cyclase but many other systems as well, leads to theoretical complications of considerable magnitude. The possibility has already been mentioned that in certain cases one second messenger could influence the production or accumulation of another second messenger, but the recognition of this as a theoretical possibility is not the same as assuming that this is always the mechanism by which adenyl cyclase is affected by hormones.
1969; Sattin and Rail, 1970). It should also be established that an active phosphodiesterase is present in the preparation being studied, and that the drug to be used is capable of inhibiting it. It is becoming clear that the properties of phosphodiesterase, like those of many other enzymes, may differ from one tissue or species to another. Although all mammalian tissues which have been studied to date contain a phosphodiesterase which is susceptible to inhibition by the methylxanthines, for example, some unicellular organisms contain an enzyme which is apparently not affected by these compounds (Brana and Chytil, 1966; Chang, 1968).
In terms of the hypothesis represented by Fig. 2, the loss of hormonal sensitivity would be equivalent to the loss of sensitivity to an allosteric effector. This is very commonly seen with allosteric enzymes, including purified aspartate transcarbamylase. In the case of the enzyme from E. coli, for example, the sensitivity to CTP can be destroyed by relatively gentle means while the catalytic activity remains largely unaffected (Gerhart and Pardee, 1963). Furthermore, if the loss of hormonal sensitivity were due simply to a physical detachment of the receptor system from the adenyl cyclase system, it might be thought that at least some restoration of sensitivity could be achieved by means of recombination experiments.