Cerebral ventricular transport and uptake: importance for CCK-mediated satiety

Brain cholecystokinin (CCK) peptides have been proposed to be involved in the control of feed intake. We have examined the importance of the cerebral ventricular system in CCK-mediated satiety in sheep. Continuous injection of 0.64 pmol/min CCK-8 into the lateral ventricles (LV) decreased feeding, whereas injection of neither 0.64 nor 2.55 pmol/min CCK-8 into the cisterna magna (CM) significantly affected feeding. Thus, it is likely that the rostral, but not caudal, ventricular compartments and/or adjacent brain areas are involved in CCK-8 mediated satiety. The rate of injection of carrier solution (synthetic cerebrospinal fluid [CSF]) was found to affect feed intake during a continuous 75 min injection: feed intakes were greater during injection of sCSF at 0.10 ml/min than during either 0.03 ml/min sCSF or no injection (sham). Injection of 0.64 pmol/min CCK-8 in either 0.03 or 0.10 ml/min decreased feeding. The increased feeding during 0.10 ml/min sCSF injection may have been due to dilution of endogenous CCK released into CSF during the meal. To determine the percent recovery from CSF of exogenous CCK-8, CSF samples from CM were collected during 3 hr continuous LV injections of CCK-8 and inulin (for measurement of bulk absorption). Only 20 to 40 percent of administered CCK-8 was recovered in CM CSF. The loss of CCK-8 was probably not due to degradation in the CSF by proteolytic enzymes, since CCK-8 concentrations did not decrease during in vitro incubation at 37 degrees C for up to 24 hr. We propose that CCK-8 is released during feeding into the ventricular system, and subsequently taken up from CSF by specialized ependymal cells for transport to sites of action.