Abstract. A heat-labile factor in cell-free filtrate of a Vibrio cholerae culture induces a marked rise in the wet-weight concentration of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) in the intestinal mucosa of the dog. The increase becomes appreciable 1-1.5 hr after intraluminal administration of the filtrate, about the same time as the onset of intestinal secretion in response to a heat-labile enterotoxin in the filtrate. These results are consistent with the hypothesis that cyclic AMP may be an intermediary in the intestinal secretory response to cholera toxin.When added to sheets of isolated rabbit ileal mucosa, adenosine 3':5'-cyclic monophosphate (cyclic AMP) induces an abrupt reversal of net chloride flux from the absorptive to the secretory direction, along with other ion-flux changes.' If water accompanies the ions isosmotically a substantial secretion of fluid should result. In vivo as well as in vitro, agents that may increase concentrations of cyclic AMP in other tissues (prostaglandins) or potentiate such elevation (theophylline) also induce net intestinal secretion of ions and, at least in vivo, of water.'4 Similar indirect evidence suggests that cyclic AMP may play a physiological role not only in intestinal secretion but also in various other gastrointestinal secretory processes.-So far as we know, however, an increase in tissue concentrations of cyclic AMP has not been demonstrated in any gastrointestinal secretory state (see note added in proof).A heat-labile enterotoxic moiety found in cell-free filtrates of Vibrio cholerae cultures evokes a profuse intestinal secretion in several species.6'7 Such filtrates are reported2 48 to have effects on intestinal ion fluxes in vitro, and on fluxes of water and ions in vivo, closely mimicking those of exogenous cyclic AMP, prostaglandins, and theophylline. It has therefore been suggested' 4 that the mechanism by which cholera enterotoxin induces intestinal secretion may involve cyclic AMP. The plausibility of this hypothesis is not diminished by recent reports that partially purified cholera enterotoxin in low concentrations also mimics one effect of cyclic AMP in a functionally quite different system, the fat cell, where it stimulates lipolysis.9 10 As yet, however, it has not been directly demonstrated that a cell-free filtrate of a V. cholerae culture can induce a rise in 851

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When rats were fed isocaloric amounts of chemically defined diets with variable amounts of protein (8-60%) or fat (0-30%) over a 10-day period, their serum and antral gastrin concentrations were, respectively, 60 and 40% lower than the levels of chow-fed rats. It was also determined that neither the low bulk content of these diets nor their inability to adequately buffer the gastric pH contributed to this response. The time course of this dietary-induced reduction in gastrin levels was investigated and it was found that the serum hormone levels were significantly reduced as early as 1-2 h after chow-fed rats were placed on these chemically defined diets. Antral gastrin levels were maintained at normal levels for 4-5 days after rats started consuming these synthetic diets and fell thereafter. With all of the chemically defined diets tested, the gastrin secretory response to a meal was significantly reduced. It therefore appears that synthetic diets lack some undefined food constituent present in chow that is required for the normal postprandial release of gastrin or, alternatively, that they contain an inhibitory factor which blocks the normal secretory response.

The purpose of the present study was to compare the small intestinal blood flow that equilibrates with luminal CO (FLco) with simultaneous determinations of villus blood flow measured by a recent modification of the microsphere technique. These studies, carried out in rabbits, showed that FLco closely correlated (r = 0.83) with villus flow measured with microspheres over a three-fold range of flows, and the mean rate of flow to the villi by both techniques was about 0.08 ml/min X g of intestine. Thus, FLco appears to be a measure of villus blood flow. Based on previous studies of inert gas uptake from the rabbit small intestine, it appears that absorption of readily diffusible substances in the rabbit can be represented by a simple two-component model: a flow-limited component in which substances equilibrate with villus blood flow and are carried away without subsequent countercurrent exchange, and a diffusion-limited component which presumably represents uptake by the blood flow of the crypt region or submucosa.