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THE EFFECTS OF H Y P O T H A L A M I C HORMONES ON CYCLO(HIS-PRO) R E C E P T O R B I N D I N G IN RAT

LIVER

N O R I O OGAWA and Y U K I K O HIROSE*, Department of N e u r o c h e m i s t r y , Institute for Neuro-

biology, O k a y a m a U n i v e r s i t y M e d i c a l School, 2-5-1, Shikatacho, O k a y a m a 700, Japan

The c h a r a c t e r i s t i c s of cyclo(His-Pro) receptors in the rat liver were studied

using 3H-labeled cyclo(His-Pro). Scatchard analysis suggested that the rat liver
membrane has a single binding site with an apparent d i s s o c i a t i o n constant of 70 nM.
Pretreatment of r e c e p t o r p r e p a r a t i o n s with soybean trypsin inhibitor increased
cyclo(His-Pro) binding, and the r e c e p t o r activity was sensitive to trypsin and
p h o s p h o l i p a s e A digestion, suggesting that protein and p h o s p h o l i p i d moeties are
essential for cyclo(His-Pro) binding. Thiol reagents reduced receptor b i n d i n g ac-
tivity, suggesting that the thiol group might be an important constituent of the
cyclo(His-Pro) binding site. Cross r e a c t i v i t i e s of TRH, TRH-analogues, L-His and
L-Pro were very low (0.2-9%). LH-RH and s o m a t o s t a t i n had no cross r e a c t i v i t y at
cyclo(His-Pro) binding sites. These findings indicate that b i n d i n g sites for
cyclo(His-Pro) in the rat liver are highly specific. After e s t a b l i s h i n g the opti-
m u m condition, the effects of h y p o t h a l a m i c hormones on liver cyclo(His-Pro) binding
were studied. Somatostatin (400 pg/kg/day, i.p. for 3 days) decreased the cyclo-
(His-Pro) binding, whereas i.p. injections of TRH and LH-RH had no effect on the
cyclo(His-Pro) binding. These findings suggest that s o m a t o s t a t i n might regulate
the cyclo(His-Pro) receptors in the liver.

THE EFFECTS OF 8-ENDORPHIN ON T H E R M O R E G U L A T I O N DURING E M O T I O N A L STRESS

KATSUHARU KUBO and SHUJI TSUZUKI*, D e p a r t m e n t of Bioregulation, Institute for

Medical Genetics, K u m a m o t o University Medical School, Kuhonji, K u m a m o t o 862, Japan

The effect of i n t r a - t h i r d v e n t r i c u l a r injection of B-endorphin (ED) on core tem-

perature (Tcore) and oxygen consumption under stress was s t u d i e d in rats which were
exposed to immobilization stress with wire mesh for 3 hours once a day for i0 days.
The stress induced a fall in Tcore and a decrease in oxygen consumption. Repeating
the stress, the h y p o t h e r m i c responses were d i m i n i s h e d day by day, and were signifi-
cantly less after the 4th day of stress. The recovery of oxygen consumption during
the stress p e r i o d o c c u r r e d after the 5th day, reaching pre-stress level after the 9th
day. ED i n d u c e d h y p e r t h e r m i a with an increase in oxygen consumption in a non-stress
state, but if injected at 1 hr of the stress p e r i o d on day 1 of stress it acted to
enhance the s t r e s s - i n d u c e d h y p o t h e r m i c responses. The e n h a n c e m e n t of h y p o t h e r m i a
by ED was a n t a g o n i z e d w i t h naloxone given 30 min after ED, as the lowered Tcore after
ED recovered up to the level of 1 hr of stress. Naloxone alone, if injected either
at 0 hr or 1 hr of stress, equally allowed a fall in Tcore and oxygen consumption
during the initial 1 hr but s u p p r e s s e d the further progress of h y p o t h e r m i a after
that. The data suggest that endogenous opioid systems may be involved in the modu-
lation of t h e r m o r e g u l a t o r y responses to stress but not in the m e d i a t i o n of stress
stimuli. In contrast, ED on day i0 of repeated stresses increased oxygen consump-
tion, which a c c e l e r a t e d recovery from hypothermia. Thus ED effects on thermoregu-
lation were d i f f e r e n t in non-stress and stress states, and further changed during
the process of adaptation to the stress. However, if ED was injected at 1 hr of
stress every day of the repeated stresses, the d i m i n i s h m e n t of h y p o t h e r m i c responses
during repeated stresses and the h y p e r t h e r m i c responses to ED which n o r m a ~ y occurred
by day i0 were not observed. Thus ED appeared to inhibit the development of adapta-
tional changes in energy m e t a b o l i s m and thermoregulation. From p r e s e n t study it is
s u g g e s t e d that ED may act to release the o r g a n i s m from precise h o m e o s t a t i c regula-
tion under stress and to inhibit the o r g a n i z a t i o n and development of a d a p t a t i o n a l
changes in the brain in response to the a c c u m u l a t i o n of the stress stimuli.