Peripheral control of drinking: gastrointestinal filling as a negative feedback signal, a theoretical and...

The studies described here investigated the hypothesis that the osmotic postingestional satiety signal proposed by McCleary operates through a mechanism related to gut filling rather than by osmotically induced shifts of fluid from osmoreceptors in the brain. A control theory model is presented, which was designed to make quantitatively explicit the hypothesis under question. The results showed that when mannitol, which is not absorbed from the intestine, is added to a highly palatable saccharin-glucose mixture, the amount of fluid consumed decreased in inverse proportion to the mannitol concentration. Mannitol was also shown to block fluid absorption from the intestine at a low concentration (approximately .070 M) and at higher concentrations to lead to a net flux of fluid into the intestinal lumen. It was also shown that mannitol in concentrations that reduced the intake of the palatable solution did not induce thirst when the animals were in water balance. It did induce thirst, however, when the animals were tested in a state of negative water balance. The results of these studies, considered as a whole, support the view that McCleary's osmotic postingestional satiety signal acts as an intestinal distention signal rather than by inducing thirst. The model is found to be reasonably accurate as a first approximation, and suggestions are made for improvements.