Cyclic AMP and gastric secretion: the illusive second messenger.

We have surveyed the literature which bears upon the contention that accumulation of intracellular cyclic AMP is a necessary intermediate event between secretagogue and secretion of acid by the stomach. In our view, the evidence in favor of this hypothesis is wanting for these three reasons: (i) the evidence does not fit with better established information about regulation of gastric secretion and about hormonal actions on the cyclic AMP system; (ii) technological problems involved in the biological preparations employed and in the assay procedures used make the evidence nearly uninterpretable; and (iii) there exists a body of contradictory evidence at least as convincing as that which favors the thesis. These three arguments against acceptance of the theory are not definitive and are not intended to dissuade investigators interested in gastric mucosal metabolism from their quest. And, although we are not at this time adherents of the preceding hypothesis, we are also not unmindful of its basic appeal, which has attracted numerous scientists into a study of the metabolic correlates of gastric acid secretion. Unfortunately the general appeal of the second messenger hypothesis is such as to make it almost a paradigm of gastric secretory physiology in the seventies, in Kuhn's sense of that word (118). The disadvantages of paradigms are that they tend to obscure negative evidence among their adherents, and they arouse controversies more marked by heat than by light.