Effects of CCK (cholecystokinin) as central satiety factor

$132 EFFECT OF GLUCOSE LOADING FOLLOWING FOOD DEPRIVlATION ON L~gALIZATION OF A~DIC FIBROBLASTGROWTH FACTOR-LIKE IM~UNOREACTIVlTY IN RA~ B~AIN. OSAMUYASUHARA", IKUO TOHYAMA~, ICHIRO AKIGUCHI', ~IROSHI KIMURAc, AND YUTAKAOOMUR~ ' D e p a r t m - - e n ~ n t ~ ~ ~ 6-06, ~DePt Anatomy. Shiqa Idai, Otsu, JWakanyaku Lab, Toyama Ika'yakudai, Toyama, Japan. Recent evidence indicates that acidic fibroblast growth factor (aFGF) in the CSF increases greatly following glucose injection after food deprivation. The significance of this phenomenon is unclear. We examined the effects of such manipulation on the localization of aFGF in rat brain by immunohistochemistry using anti-aFGF antisera. Ten male Wistar rats were deprived of food for 24 hours. Five of the rats were k i l l e d as a food-deprived group. The other five as a glucose loaded group were given glucose (150 mg/kg, i.p.) and fed ad libitum for 2-3 hours before sacrifice. Five non-treated rats were used as controls. In both control and food-deprived rats aFGF-like immunoreactivity was localized in subpopulations of ependymal c e l l s , tanycytes and g l i a l cells. The most intense immunostaining was observed in many c e l l s of the subfornical organ. In the glucose-loaded animals a reduction in immunoreactivity of the ependymal c e l l s was observed together with an increase in both the intensity and number of immunopositive g l i a l calls. Positive staining also became v i s i b l e in some neuronal c e l l s , including aminergic c e l l s in the brainstem and large neurons in the lateral hypothalamus. In situ hybridization histochemistry using a biotinylated oligonucleotide probe demonstrated that the mRNAof aFGF was localized in ependymal and g l i a l cells. This c l e a r l y indicates that aFGF is synthesized in these non-neuronal cells. Thus, extraneurally produced aFGF may be transferred to neuronal c e l l s under certain conditions possibly related to appetite control mechanisms.

EFFECTS

OF

CCK

(CHOLECYSTOKININ)

AS

CENTRAL

SATIETY

FACTOR

TAKEMASA SHIRAISHI t Department of Physiolo$y, Tokai University School of Medicine t Bohseidai, Isehara 259-11, Japan CCK and its derivatives have potent feeding inhibitory effects, even after vagotomy. This effect is thus considered peripheral. Recently, however, the vagal gastric branch was reported to essentially bring into full play the feeding inhibition. The present study found that CCK-8 significantly, dose-dependently i n h i b i t e d the l a t e r a l h y p o t h a l a m u s , the f e e d i n g c e n t e r , w h e n e l e c t r i c a l s t i m u l a t i o n i n d u c e d f e e d i n g ( L H A - E I F ) in the c h r o n i c rat. CCK-8s were administered in the third cerebroventricle (lll-cv). This inhibition by CCK-8 was not affected by systemic pretreatment with proglumide (i mg), a selective antagonist of CCK, while CCK (250 ng) simultaneously microinjected into lll-cv with proglumide (5 ~g) almost completely eliminated CCK's effect on the LHA-EIF. Neuronal activity of the ventromedial hypothalamus (VMH) as satiety center was enhanced, and that of the LHA was suppressed by electrophoretic direct application of CCK-8 in urethane-chloralose anesthetized rats. CCK also markedly decreased the irritability threshold of VMH glucose responding neurons. These results indicate that the satiety effect of CCK is not only peripheral, but might also be central, especially through the feeding-related h y p o t h a l a m i c neurons. They probably play an important role in the feeding inhibitory system.