Regulatory actions of acidic and basic fibroblast growth factors on food intake

$116

REGULATORY

ACTIONS

OF ACIDIC AND BASIC FIBROBLAST GROWTH FACTORS ON FOOD INTAKE.

KAZUO

SASAKI~

YUTAKA OOMURAIt KENJI SUZUKI~11AIJUN LI"I t KAZUMITSU HANAI~211KU0 TOOYAMA31HIROSHI KIMURA3r NOBORU 9~O-O1,

YANAIHARA 4,

Sci. Instru. Ctr., IInst. Wakan-Yaku, Toyama Med. & Pharmaceu.

AND

Univ. r To~ama

2Dept. Biol. T Fac. Sci.~ Kyushu Univ., Fukuoka 812, 3Inst. Nolec. Neurobiol.~ Shi~a

Univ.

Ned. Sci. I Shiga 520-211 and 4 Sch. Pharmaceu. Sci., Shizuoka Univ., Shizuoka 4221 Japan. The relations between acidic and basic fibroblast growth factors (aFGF and bFGF,

respectively),

and food intake were studied. Infusions of aFGF and bFGF into the third cerebral ventricle of

rats

dose-dependently

suppressing

food

decreased

food

intake.

Infusions

intake,

whereas

decreased food intake, aFGF was 1.5 times as potent as bFGF in of aFGFI_15 , a synthetic amino-terminal peptide of aFGF, also those of aFGF114_140, a synthetic carbomy-terminal of aFGF, had

no

potency of aFGFI_I5 on feeding inhibition was about 1/150 compared to the same molar of

aFGF. Anti-aFGF, -bFGF, and -aFGF1_15 antibodies infused into the lateral

effect.

The

concentration

hypothalamus

(LHA)

increased food intake. The results suggest that FGFs act as feeding suppressants, possively through the LHA, and that the active site of aFGF on feeding inhibition is the amino-terminal portion.

C C K C E N T R A L S A T I E T Y E F F E C T S M E D I A T E D B Y T W O I{YPOTHAI2kMIC CCK-RECEPTOKS. TAKEMASA SHIRAISHI, Department of P h y s i o l o g y , Tokal University School of Medlclne. Isehara 259-11, Japan. C h o l e c y s t o k l n l n octapeptlde (CCK-8) has been shown b e h a v i o r a l l y and electrop h y s i o l o g i c a l l y to m e d l a t e satiety through the central nervous system (CNS). This study was to identify slte(s) of action of CCK-8 on f e e d i n g related neurons in the lateral h y p o t h a l a m u s (LHA) by a n a l y z i n g electrical s t i m u l a t i o n Indue0ed f e e d i n g (LHA-ESIF) of chronic sated male W l s t a r - S P F rats In the day light. CCK-8 was a d m i n i s t e r e d Into the LHA and the v e n t r o m e d l a l h y p o t h a l a m u s (VMH) w i t h and w i t h o u t Its selective antagonists. L H A - E S I F was s i g n i f i c a n t l y (p<0.05) inhibited by 150 ng CCK-8 m l c r o l n J e c t e d Into the LHA. Thls inhibition was a b o l i s h e d by 800 ng p r o g l u m l d e (PG). a n o n s p e c l f l c CCK-8 antagonist, but not by 500 n g L-364.718 w h i c h Is a specific CCK B-type antagonist. The CCK receptors In the L H A p r o b a b l y n o n s p e c l f l c A/B type. T h e s e receptors predominate over the B-type. M i c r o l n J e c t l o n of CCK-8 Into the VbllI also suppressed LHA-ESIF. L-364,718 without CCK-8 enhanced L H A - E S I F s i g n i f i c a n t l y more than PG. and It with CCK-8 was almost c o m p l e t e l y e l i m i n a t e d CCK's effects. CCK-reeeptors in the VbIH are thus p r e d o m i n a n t l y B-type. Results suggest that CCK-8 mediates satiety through the CNS by b i n d i n g to B-type receptors to depolarize VMH f e e d i n g related neurons and increase their excita b i l i t y to inhibit feeding, and/or through A/B type receptors to h y p e r p o l a r l z e LHA f e e d i n g related neurons and decrease their e x c i t a b i l i t y to inhibit feeding.

29. Neurotoxicology LOCALIZATION OF M n - S U P E R O X I D E DISMUTASE (Mn-SOD) IN T H E R A T F O R E B R A I N : C O E X I S T E N C E WITH CHOLINE A C E T Y L T R A N S F E R A S E AND SOMATOSTATIN, SHINOBU INAGAKI , A K I H I K O OHTA r KEI M A C H I D A , K E I C H I R O SUZUKI t NAOYUKI TANIGUCHI z__AND HIROSHI TAKAGI , Department of A n a t o m y r Osaka City U n i v e r s i t y Medical School r Abeno-ku, O s a k a t 545 ( J a p a n ) , D e p a r t m e n t of B i o c h e m i s t r y , Osaka University Medical School, Kita-ku, Osaka, 530 (Japan). Superoxide dismutase (SOD) c a t a l y z e s the c o n v e r s i o n of the s u p e r o x i d e radicals to hydrogen peroxide and molecular oxygen, and it is suggested that SOD protects cells against the potential toxicity of reactive free radicals produced from oxygen. The i m m u n o h i s t o c h e m i c a l localization of manganese (Mn)-SOD was studied in t h e r a t f o r e b r a i n by using polyclonal antisera to M n - S O D . I m m u n o s t a i n i n g was intense in neurons of the m a g n o c e l l u l a r basal nucleus, CA3 pyramidal cells and n o n - p y r a m i d a l cells of all subfields in the hippocampus, large-sized and several m e d i u m - s i z e d neurons in the neostriatum, pyramidal and n o n - p y r a m i d a l c e l l s of l a y e r V a n d VI in the n e o c o r t e x , r e t i c u l a r t h a l a m i c neurons and many h y p o t h a l a m i c neurons, whereas it was moderate to weak in other cells. Double immunostaining with monoclonal antisera to choline a c e t y l t r a n s f e r a s e or s o m a t o s t a t i n d e m o n s t r a t e d that cholinergic m a g n o c e l l u l a r basal neurons and large-sized neurons in the n e o s t r i a t u m contained high levels of Mn-SOD, and several s o m a t o s t a t i n immunoreactive neurons in the forebrain were also intensely immunoreactive to Mn-SOD.